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                          "autores" => array:3 [
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                            1 => "P Gibson"
                            2 => "J Pekkanen"
                            3 => "N Pearce"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2002"
                        "volumen" => "57"
                        "paginaInicial" => "643"
                        "paginaFinal" => "648"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12096210"
                            "web" => "Medline"
                          ]
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                          "pii" => "S0161642009014171"
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                          "issn" => "01616420"
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                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structural changes in airway diseases&#58; characteristics&#44; mechanisms&#44; consequences&#44; and pharmacologic modulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C Bergeron"
                            1 => "LP Boulet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.129.4.1068"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "129"
                        "paginaInicial" => "1068"
                        "paginaFinal" => "1087"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16608960"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "WV Filley"
                            1 => "KE Holley"
                            2 => "GM Kephart"
                            3 => "GJ Gleich"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1982"
                        "volumen" => "2"
                        "paginaInicial" => "11"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2898621"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The injurious effect of eosinophil peroxidase&#44; hydrogen peroxide&#44; and halides on pneumocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "JM Agosti"
                            1 => "LC Altman"
                            2 => "GH Ayars"
                            3 => "DA Loegering"
                            4 => "GJ Gleich"
                            5 => "SJ Klebanoff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1987"
                        "volumen" => "79"
                        "paginaInicial" => "496"
                        "paginaFinal" => "504"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3029204"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biology of eosinophils"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H Kita"
                            1 => "CR Adolphosn"
                            2 => "GJ Gleich"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "titulo" => "Allergy&#58; principles and practice"
                        "paginaInicial" => "305"
                        "paginaFinal" => "332"
                        "edicion" => "6th ed&#46;"
                        "serieFecha" => "2003"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mast cells&#44; basophils&#44; and eosinophils&#58; distinct but overlapping pathways for recruitment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "BS Bochner"
                            1 => "RP Schleimer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Rev"
                        "fecha" => "2001"
                        "volumen" => "179"
                        "paginaInicial" => "5"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11292027"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Verdict in the case of therapies versus eosinophils&#58; the jury is still out"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "BS Bochner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2003.09.046"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "paginaInicial" => "3"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14713900"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Time to death&#44; airway wall inflammation and remodeling in fatal asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "AL James"
                            1 => "JG Elliot"
                            2 => "MJ Abramson"
                            3 => "EH Walters"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.05.00146404"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "429"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16135723"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G Cox"
                            1 => "J Crossley"
                            2 => "Z Xing"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.12.2.7865221"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "1995"
                        "volumen" => "12"
                        "paginaInicial" => "232"
                        "paginaFinal" => "237"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7865221"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0886335010008576"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neutrophilic inflammation&#59; &#8220;Don&#39;t you go to pieces on me&#33;&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "RA Stockley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.06.00053906"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2006"
                        "volumen" => "28"
                        "paginaInicial" => "257"
                        "paginaFinal" => "258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16880362"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-IL-5 receptor antibody&#44; but not anti-IL-5 antibody&#44; inhibits airway hyperresponsiveness in murine model of chronic asthma &#91;abstract&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K Sugiyama"
                            1 => "G Cheng"
                            2 => "Y Aoki"
                            3 => "T Fukuda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "167"
                        "paginaInicial" => "A494"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "CA Rizzo"
                            1 => "R Yang"
                            2 => "S Greenfeder"
                            3 => "RW Egan"
                            4 => "RA Pauwels"
                            5 => "JA Hey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2002"
                        "volumen" => "109"
                        "paginaInicial" => "404"
                        "paginaFinal" => "409"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11897983"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The changing cigarette&#44; 1950-1995"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D Hoffmann"
                            1 => "I Hoffmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/009841097160393"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Toxicol Environ Health"
                        "fecha" => "1997"
                        "volumen" => "50"
                        "paginaInicial" => "307"
                        "paginaFinal" => "364"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9120872"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COPD and tobacco smoke"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M Bartal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4081/monaldi.2005.623"
                      "Revista" => array:6 [
                        "tituloSerie" => "Monaldi Arch Chest Dis"
                        "fecha" => "2005"
                        "volumen" => "63"
                        "paginaInicial" => "213"
                        "paginaFinal" => "225"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16454221"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Direct evidence of secondary necrosis of neutrophils during intense lung inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K Rydell-T&#246;rm&#228;nen"
                            1 => "L Uller"
                            2 => "JS Erjefalt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.06.00126905"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2006"
                        "volumen" => "28"
                        "paginaInicial" => "268"
                        "paginaFinal" => "274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16510453"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0002939410008408"
                          "estado" => "S300"
                          "issn" => "00029394"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "BWM Willemse"
                            1 => "NHT Ten Hacken"
                            2 => "B Rutgers"
                            3 => "IGAT Lesman-Leegte"
                            4 => "DS Postma"
                            5 => "W Timens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.05.00108904"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "835"
                        "paginaFinal" => "845"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16264044"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0886335010014240"
                          "estado" => "S300"
                          "issn" => "08863350"
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                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G Viegi"
                            1 => "I Annesi"
                            2 => "G Matteelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir Mon"
                        "fecha" => "2003"
                        "volumen" => "23"
                        "paginaInicial" => "1"
                        "paginaFinal" => "25"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "State-specific prevalence of current cigarette smoking among adults&#58; United States&#44; 2002"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Centers for Disease Control and Prevention"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "MMWR Morb Mortal Wkly Rep"
                        "fecha" => "2004"
                        "volumen" => "52"
                        "paginaInicial" => "1277"
                        "paginaFinal" => "1300"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14712175"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationships of active smoking to asthma and asthma severity in the EGEA study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "V Siroux"
                            1 => "I Pin"
                            2 => "MP Oryszcyn"
                            3 => "N Le Moual"
                            4 => "F Kauffmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2000"
                        "volumen" => "15"
                        "paginaInicial" => "470"
                        "paginaFinal" => "477"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10759439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cigarette smoking among asthmatics adults presenting to 64 emergency departments"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "RA Silverman"
                            1 => "ED Boudreaux"
                            2 => "PG Woodruff"
                            3 => "S Clark"
                            4 => "CA Camargo Jr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2003"
                        "volumen" => "123"
                        "paginaInicial" => "1472"
                        "paginaFinal" => "1479"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12740263"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asthma and cigarette smoking"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "NC Thomson"
                            1 => "R Chaudhuri"
                            2 => "E Livingston"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.04.00039004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2004"
                        "volumen" => "24"
                        "paginaInicial" => "822"
                        "paginaFinal" => "833"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15516679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Onset and remission of allergic rhinitis and asthma and the relationship with atopic sensitization and smoking"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P Plaschke"
                            1 => "C Janson"
                            2 => "E Norman"
                            3 => "E Bjornsson"
                            4 => "S Ellbjar"
                            5 => "B Jarvholm"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.3.9912030"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "920"
                        "paginaFinal" => "924"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10988106"
                            "web" => "Medline"
                          ]
                        ]
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                          "pii" => "S0886335010017700"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asthma phenotypes according to the timing of smoking onset in young adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C Raherison"
                            1 => "I Baldi"
                            2 => "J Tunon de Lara"
                            3 => "A Taytard"
                            4 => "I Annesi-Maesano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Tuberc Lung Dis"
                        "fecha" => "2003"
                        "volumen" => "7"
                        "paginaInicial" => "84"
                        "paginaFinal" => "92"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12701840"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Associations of smoking with hospital-based care and quality of life in patients with obstructive airway disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "JM Sippel"
                            1 => "KL Pedula"
                            2 => "WM Vollmer"
                            3 => "AS Buist"
                            4 => "ML Osborne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1999"
                        "volumen" => "115"
                        "paginaInicial" => "691"
                        "paginaFinal" => "696"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10084477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bronchial reactivity to cigarette smoke&#59; relation to lung function&#44; respiratory symptoms&#44; serum-immunoglobulin E and blood eosinophil and leukocyte counts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E Jensen"
                            1 => "R Dahl"
                            2 => "F Steffensen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/rmed.1999.0664"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2000"
                        "volumen" => "94"
                        "paginaInicial" => "119"
                        "paginaFinal" => "127"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10714416"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Airway responsiveness to adenosine 5&#39;-monophophate in smokers and nonsmokers with atopic asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y Oosterhoff"
                            1 => "M Jansen"
                            2 => "D Postma"
                            3 => "G Koeter"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1993"
                        "volumen" => "92"
                        "paginaInicial" => "773"
                        "paginaFinal" => "776"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8227870"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of gender on hospital admissions for asthma and prevalence of self-reported asthma&#58; a prospective study based on a sample of the general population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E Prescott"
                            1 => "P Lange"
                            2 => "J Vestbo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "1997"
                        "volumen" => "52"
                        "paginaInicial" => "287"
                        "paginaFinal" => "289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9093349"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Near-fatal asthma&#58; a population-based study of risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I Mitchell"
                            1 => "S Tough"
                            2 => "L Semple"
                            3 => "F Green"
                            4 => "P Hessel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2002"
                        "volumen" => "121"
                        "paginaInicial" => "1407"
                        "paginaFinal" => "1413"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12006421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early life factors contribute to the decrease in lung function between ages 18 and 40&#58; the Coronary Artery Risk Development in Young Adults study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "GG Apostol"
                            1 => "DR Jacobs"
                            2 => "AW Tsai"
                            3 => "RS Crow"
                            4 => "OD Williams"
                            5 => "MC Townsend"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.2007035"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "paginaInicial" => "166"
                        "paginaFinal" => "172"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12119228"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0886335011011175"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute effects of cigarette smoking on inflammation in healthy intermittent smokers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H van der Vaart"
                            1 => "DS Postma"
                            2 => "W Timens"
                            3 => "MN Hylkema"
                            4 => "BW Willemse"
                            5 => "HM Boezen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1465-9921-6-22"
                      "Revista" => array:5 [
                        "tituloSerie" => "Respir Res"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15740629"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R Chaudhuri"
                            1 => "E Livingston"
                            2 => "AD McMahon"
                            3 => "L Thomson"
                            4 => "W Borland"
                            5 => "NC Thomson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200304-503OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2003"
                        "volumen" => "168"
                        "paginaInicial" => "1308"
                        "paginaFinal" => "1311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12893649"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of smoking on asthma therapy&#58; a critical review of clinical evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E Livingston"
                            1 => "NC Thomson"
                            2 => "GW Chalmers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Drugs"
                        "fecha" => "2005"
                        "volumen" => "65"
                        "paginaInicial" => "1521"
                        "paginaFinal" => "1536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16033290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cigarette smoking in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T Higenbotam"
                            1 => "C Feyeraband"
                            2 => "T Clark"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dis Chest"
                        "fecha" => "1980"
                        "volumen" => "74"
                        "paginaInicial" => "279"
                        "paginaFinal" => "284"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7426367"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cigarette smoking and incidence of chronic bronchitis and asthma in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R Troisi"
                            1 => "F Speizer"
                            2 => "B Rosner"
                            3 => "D Trichopoulos"
                            4 => "W Willet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1995"
                        "volumen" => "108"
                        "paginaInicial" => "1557"
                        "paginaFinal" => "1561"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7497760"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of eosinophil apoptosis by nitric oxide&#58; role of c-Jun-N-terminal kinase and signal transducer and activator of transcription 5"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X Zhang"
                            1 => "E Moilanen"
                            2 => "A Lahti"
                            3 => "M Hamalainen"
                            4 => "MA Giembycz"
                            5 => "PJ Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2003"
                        "volumen" => "112"
                        "paginaInicial" => "93"
                        "paginaFinal" => "101"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12847485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Smoking and airway inflammation in patients with mild asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "GW Chalmers"
                            1 => "KJ McLeod"
                            2 => "L Thomson"
                            3 => "SA Little"
                            4 => "C McSharry"
                            5 => "NC Thomson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "120"
                        "paginaInicial" => "1917"
                        "paginaFinal" => "1922"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11742922"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of cigarette smoke on exhaled nitric oxide in mild steroid-naive asthmatics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G Verleden"
                            1 => "L Dupont"
                            2 => "A Verpeut"
                            3 => "M Demedts"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1999"
                        "volumen" => "116"
                        "paginaInicial" => "59"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10424504"
                            "web" => "Medline"
                          ]
                        ]
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                          "pii" => "S0886335008007888"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
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                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Short and long-term effects of cigarette smoking independently influence exhaled nitric oxide concentration in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "CP McSharry"
                            1 => "IC McKay"
                            2 => "R Chaudhuri"
                            3 => "E Livingston"
                            4 => "I Fraser"
                            5 => "NC Thomson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2005.03.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2005"
                        "volumen" => "116"
                        "paginaInicial" => "88"
                        "paginaFinal" => "93"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15990779"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib48"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differences in interleukin 8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease and asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "V Keatings"
                            1 => "P Collins"
                            2 => "D Scott"
                            3 => "P Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.153.2.8564092"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1996"
                        "volumen" => "153"
                        "paginaInicial" => "530"
                        "paginaFinal" => "534"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8564092"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib49"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-&#91;&#46;alpha&#93; release"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Churg"
                            1 => "RD Wang"
                            2 => "H Tai"
                            3 => "X Wang"
                            4 => "C Xie"
                            5 => "J Dai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200212-1396OC"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2003"
                        "volumen" => "167"
                        "paginaInicial" => "1083"
                        "paginaFinal" => "1089"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12522030"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0886335010006255"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib50"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association of smoking with sensitization to common environmental allergens&#58; results from the European Community Health Survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D Jarvis"
                            1 => "S Chinn"
                            2 => "C Lucynska"
                            3 => "P Burney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1999"
                        "volumen" => "104"
                        "paginaInicial" => "934"
                        "paginaFinal" => "940"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10550735"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib51"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy&#44; pulmonary function&#44; and high-resolution computed tomography lung densitometry in elderly patients with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F Mitsunobu"
                            1 => "K Ashida"
                            2 => "Y Hosaki"
                            3 => "Y Hosaki"
                            4 => "H Tsugeno"
                            5 => "M Okamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Exp Allergy"
                        "fecha" => "2004"
                        "volumen" => "34"
                        "paginaInicial" => "59"
                        "paginaFinal" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14720263"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0886335008004082"
                          "estado" => "S300"
                          "issn" => "08863350"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib52"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute effects of cigarette smoke on inflammation and oxidative stress&#58; a review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H van der Vaart"
                            1 => "DS Postma"
                            2 => "W Timens"
                            3 => "NHT ten Hacken"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2003.012468"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "713"
                        "paginaFinal" => "721"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15282395"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib53"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "JEM Tomlinson"
                            1 => "AD McMahon"
                            2 => "R Chaudhuri"
                            3 => "JM Thompson"
                            4 => "SF Wood"
                            5 => "NC Thomson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2004.033688"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2005"
                        "volumen" => "60"
                        "paginaInicial" => "282"
                        "paginaFinal" => "287"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15790982"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib54"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influence of smoking on the treatment response in patients with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "NC Thomson"
                            1 => "M Spears"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Curr Opin Allergy Clin Immunol"
                        "fecha" => "2005"
                        "volumen" => "5"
                        "paginaInicial" => "57"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15643345"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S000293940900097X"
                          "estado" => "S300"
                          "issn" => "00029394"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib55"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Corticosteroids&#58; the drugs to beat"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "PJ Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejphar.2005.12.052"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pharmacol"
                        "fecha" => "2006"
                        "volumen" => "533"
                        "paginaInicial" => "2"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16436275"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib56"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An ongoing confidential enquiry into asthma deaths in the Eastern region of the UK&#44; 2001-2003"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B Harrison"
                            1 => "P Stephenson"
                            2 => "G Mohan"
                            3 => "S Nasser"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pcrj.2005.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prim Care Respir J"
                        "fecha" => "2005"
                        "volumen" => "14"
                        "paginaInicial" => "303"
                        "paginaFinal" => "313"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16701746"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
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Vol. 43. Issue 6.
Pages 340-345 (January 2007)
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Vol. 43. Issue 6.
Pages 340-345 (January 2007)
Review Article
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Asthma and Smoking: An Unfortunate Combination
Visits
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Jesús Bellido Casado
Corresponding author
jbellido@santpau.es

Correspondence: Dr. J. Bellido Casado. Departamento de Neumología, Hospital de la Santa Creu i Sant Pau. Sant Antoni M. Claret, 167. 08025 Barcelona. España
Departamento de Neumología, Hospital de la Santa Creu i Sant Pau, Facultad de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain
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Asthma is an inflammatory disease of the airways in which a key role is played by certain cells and mediators (T-helper 2 cells, mast cells, eosinophils, interleukin 4 and 5). In certain disorders, such as irritant-induced asthma, reactive airways dysfunction syndrome, and asthma due to toluene diisocyanate, inflammation is mediated predominantly by T-helper 1 cells, macrophages and neutrophils. Smoking also produces bronchial inflammation, in this case mediated primarily by macrophages and neutrophils although eosinophil predominance has also been observed in some smokers (an allergic response to certain antigens). The remodeling of the airway wall that accompanies the chronic inflammatory cascade may alter the cell response profile making it difficult to determine which type of inflammatory infiltrate is predominant. The association of asthma and smoking is a reality in our society, and it is a combination that substantially modifies pathogenic mechanisms and gives rise to a more severe clinical picture. Resistance to some of the pharmacotherapies used routinely in the treatment of asthma (corticosteroids) has also been observed and this has favored the use of other drugs (antileukotrienes). One of the preventative measures that should be used more energetically is to encourage patients to stop smoking, paying particular attention to asthmatic smokers.

Key words:
Asthma
Smoking
Inflammation
Eosinophils
Neutrophils
Prevention

El asma es una enfermedad inflamatoria de las vías aéreas en la que desempeñan un papel primordial determinadas células y mediadores (linfocitos T helper -2, mastocitos, eosinófilos, interleucinas-4 y 5). En algunas situaciones la inflamación predominante está mediada por linfocitos T helper -1, macrófagos y neutrófilos, como en el asma por irritantes, el síndrome de disfunción reactiva de las vías aéreas, el asma por diisocianato de tolueno (TDI), etc. Por otra parte, también el tabaco produce inflamación bronquial, fundamentalmente mediada por macrófagos y neutrófilos, aunque en algunos fumadores se observa también un predominio de eosinófilos (respuesta inmunoalérgica a determinados antígenos). El remodelado bronquial que acompaña a la cascada inflamatoria crónica puede modificar la respuesta celular y confundir sobre el predominio de uno u otro tipo de infiltrado inflamatorio. La asociación de asma y tabaco constituye una realidad en nuestro medio, a la vez que modifica sustancialmente los mecanismos patogénicos, produce una clínica más florida y se observa resistencia a ciertos tratamientos habituales en el asma (corticoides), lo que ha propiciado la utilización de otros fármacos (antileucotrienos). Una de las medidas preventivas que deben utilizarse con más energía es propiciar el abandono del hábito tabáquico, prestando especial atención a los asmáticos fumadores.

Palabras clave:
Asma
Tabaco
Inflamación
Eosinófilos
Neutrófilos
Prevención
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REFERENCES
[1]
V Plaza, FJ Álvarez, P Casan, N Cobos, A López Viña, MA Llauger, et al.
en calidad de Comité Ejecutivo de la GEMA y en representación del grupo de redactores. Guía Española para el Manejo del Asma (GEMA).
Arch Bronconeumol, 39 (2003), pp. 1-42
[2]
The Lancet editors.
A plea to abandon asthma as a disease concept.
[3]
SE Wenzel.
Asthma: defining of the persistent adult phenotypes.
[4]
DJ Pierson.
Clinical practice guidelines for chronic obstructive pulmonary disease: a review and comparison of current resources.
Respir Care, 51 (2006), pp. 277-288
[5]
FE Hargreave, K Parameswaran.
Asthma, COPD and bronchitis are just components of airway disease.
Eur Respir J, 28 (2006), pp. 264-267
[6]
JW Steinke, L Borish.
Cytokines and chemokines.
J Allergy Clin Immunol, 117 (2006), pp. 441-445
[7]
C Boxall, ST Holgate, DE Davies.
The contribution of transforming growth factor-beta and epidermal growth factor signalling to airway remodelling in chronic asthma.
Eur Respir J, 27 (2006), pp. 208-229
[8]
AJM van Oosterhout, N Bloksma.
Regulatory T-lymphocytes in asthma.
Eur Respir J, 26 (2005), pp. 918-932
[9]
N Carroll, C Cooke, A Jamnes.
The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics.
Eur Respir J, 10 (1997), pp. 292-300
[10]
J Douwes, P Gibson, J Pekkanen, N Pearce.
Non-eosinophilic asthma: importance and possible mechanism.
Thorax, 57 (2002), pp. 643-648
[11]
C Bergeron, LP Boulet.
Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation.
Chest, 129 (2006), pp. 1068-1087
[12]
WV Filley, KE Holley, GM Kephart, GJ Gleich.
Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma.
Lancet, 2 (1982), pp. 11-15
[13]
JM Agosti, LC Altman, GH Ayars, DA Loegering, GJ Gleich, SJ Klebanoff.
The injurious effect of eosinophil peroxidase, hydrogen peroxide, and halides on pneumocytes.
J Allergy Clin Immunol, 79 (1987), pp. 496-504
[14]
H Kita, CR Adolphosn, GJ Gleich.
Biology of eosinophils.
Allergy: principles and practice, 6th ed., pp. 305-332
[15]
BS Bochner, RP Schleimer.
Mast cells, basophils, and eosinophils: distinct but overlapping pathways for recruitment.
Immunol Rev, 179 (2001), pp. 5-15
[16]
BS Bochner.
Verdict in the case of therapies versus eosinophils: the jury is still out.
J Allergy Clin Immunol, 113 (2004), pp. 3-9
[17]
AL James, JG Elliot, MJ Abramson, EH Walters.
Time to death, airway wall inflammation and remodeling in fatal asthma.
Eur Respir J, 26 (2005), pp. 429-434
[18]
G Cox, J Crossley, Z Xing.
Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo.
Am J Respir Cell Mol Biol, 12 (1995), pp. 232-237
[19]
RA Stockley.
Neutrophilic inflammation; “Don't you go to pieces on me!”.
Eur Respir J, 28 (2006), pp. 257-258
[20]
K Sugiyama, G Cheng, Y Aoki, T Fukuda.
Anti-IL-5 receptor antibody, but not anti-IL-5 antibody, inhibits airway hyperresponsiveness in murine model of chronic asthma [abstract].
Am J Respir Crit Care Med, 167 (2002), pp. A494
[21]
CA Rizzo, R Yang, S Greenfeder, RW Egan, RA Pauwels, JA Hey.
The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness.
J Allergy Clin Immunol, 109 (2002), pp. 404-409
[22]
D Hoffmann, I Hoffmann.
The changing cigarette, 1950-1995.
J Toxicol Environ Health, 50 (1997), pp. 307-364
[23]
M Bartal.
COPD and tobacco smoke.
Monaldi Arch Chest Dis, 63 (2005), pp. 213-225
[24]
K Rydell-Törmänen, L Uller, JS Erjefalt.
Direct evidence of secondary necrosis of neutrophils during intense lung inflammation.
Eur Respir J, 28 (2006), pp. 268-274
[25]
BWM Willemse, NHT Ten Hacken, B Rutgers, IGAT Lesman-Leegte, DS Postma, W Timens.
Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers.
Eur Respir J, 26 (2005), pp. 835-845
[26]
G Viegi, I Annesi, G Matteelli.
Epidemiology of asthma.
Eur Respir Mon, 23 (2003), pp. 1-25
[27]
Centers for Disease Control and Prevention.
State-specific prevalence of current cigarette smoking among adults: United States, 2002.
MMWR Morb Mortal Wkly Rep, 52 (2004), pp. 1277-1300
[28]
V Siroux, I Pin, MP Oryszcyn, N Le Moual, F Kauffmann.
Relationships of active smoking to asthma and asthma severity in the EGEA study.
Eur Respir J, 15 (2000), pp. 470-477
[29]
RA Silverman, ED Boudreaux, PG Woodruff, S Clark, CA Camargo Jr.
Cigarette smoking among asthmatics adults presenting to 64 emergency departments.
Chest, 123 (2003), pp. 1472-1479
[30]
NC Thomson, R Chaudhuri, E Livingston.
Asthma and cigarette smoking.
Eur Respir J, 24 (2004), pp. 822-833
[31]
P Plaschke, C Janson, E Norman, E Bjornsson, S Ellbjar, B Jarvholm.
Onset and remission of allergic rhinitis and asthma and the relationship with atopic sensitization and smoking.
Am J Respir Crit Care Med, 162 (2000), pp. 920-924
[32]
C Raherison, I Baldi, J Tunon de Lara, A Taytard, I Annesi-Maesano.
Asthma phenotypes according to the timing of smoking onset in young adults.
Int J Tuberc Lung Dis, 7 (2003), pp. 84-92
[33]
JM Sippel, KL Pedula, WM Vollmer, AS Buist, ML Osborne.
Associations of smoking with hospital-based care and quality of life in patients with obstructive airway disease.
Chest, 115 (1999), pp. 691-696
[34]
E Jensen, R Dahl, F Steffensen.
Bronchial reactivity to cigarette smoke; relation to lung function, respiratory symptoms, serum-immunoglobulin E and blood eosinophil and leukocyte counts.
Respir Med, 94 (2000), pp. 119-127
[35]
Y Oosterhoff, M Jansen, D Postma, G Koeter.
Airway responsiveness to adenosine 5'-monophophate in smokers and nonsmokers with atopic asthma.
J Allergy Clin Immunol, 92 (1993), pp. 773-776
[35]
E Prescott, P Lange, J Vestbo.
Effect of gender on hospital admissions for asthma and prevalence of self-reported asthma: a prospective study based on a sample of the general population.
Thorax, 52 (1997), pp. 287-289
[36]
I Mitchell, S Tough, L Semple, F Green, P Hessel.
Near-fatal asthma: a population-based study of risk factors.
Chest, 121 (2002), pp. 1407-1413
[37]
GG Apostol, DR Jacobs, AW Tsai, RS Crow, OD Williams, MC Townsend, et al.
Early life factors contribute to the decrease in lung function between ages 18 and 40: the Coronary Artery Risk Development in Young Adults study.
Am J Respir Crit Care Med, 166 (2002), pp. 166-172
[38]
H van der Vaart, DS Postma, W Timens, MN Hylkema, BW Willemse, HM Boezen, et al.
Acute effects of cigarette smoking on inflammation in healthy intermittent smokers.
Respir Res, 6 (2005), pp. 22
[39]
R Chaudhuri, E Livingston, AD McMahon, L Thomson, W Borland, NC Thomson.
Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma.
Am J Respir Crit Care Med, 168 (2003), pp. 1308-1311
[40]
E Livingston, NC Thomson, GW Chalmers.
Impact of smoking on asthma therapy: a critical review of clinical evidence.
Drugs, 65 (2005), pp. 1521-1536
[41]
T Higenbotam, C Feyeraband, T Clark.
Cigarette smoking in asthma.
Br J Dis Chest, 74 (1980), pp. 279-284
[42]
R Troisi, F Speizer, B Rosner, D Trichopoulos, W Willet.
Cigarette smoking and incidence of chronic bronchitis and asthma in women.
Chest, 108 (1995), pp. 1557-1561
[43]
X Zhang, E Moilanen, A Lahti, M Hamalainen, MA Giembycz, PJ Barnes, et al.
Regulation of eosinophil apoptosis by nitric oxide: role of c-Jun-N-terminal kinase and signal transducer and activator of transcription 5.
J Allergy Clin Immunol, 112 (2003), pp. 93-101
[44]
GW Chalmers, KJ McLeod, L Thomson, SA Little, C McSharry, NC Thomson.
Smoking and airway inflammation in patients with mild asthma.
Chest, 120 (2001), pp. 1917-1922
[46]
G Verleden, L Dupont, A Verpeut, M Demedts.
The effect of cigarette smoke on exhaled nitric oxide in mild steroid-naive asthmatics.
Chest, 116 (1999), pp. 59-64
[47]
CP McSharry, IC McKay, R Chaudhuri, E Livingston, I Fraser, NC Thomson.
Short and long-term effects of cigarette smoking independently influence exhaled nitric oxide concentration in asthma.
J Allergy Clin Immunol, 116 (2005), pp. 88-93
[48]
V Keatings, P Collins, D Scott, P Barnes.
Differences in interleukin 8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease and asthma.
Am J Respir Crit Care Med, 153 (1996), pp. 530-534
[49]
A Churg, RD Wang, H Tai, X Wang, C Xie, J Dai, et al.
Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-[.alpha] release.
Am J Respir Crit Care Med, 167 (2003), pp. 1083-1089
[50]
D Jarvis, S Chinn, C Lucynska, P Burney.
The association of smoking with sensitization to common environmental allergens: results from the European Community Health Survey.
J Allergy Clin Immunol, 104 (1999), pp. 934-940
[51]
F Mitsunobu, K Ashida, Y Hosaki, Y Hosaki, H Tsugeno, M Okamoto, et al.
Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy, pulmonary function, and high-resolution computed tomography lung densitometry in elderly patients with asthma.
Clin Exp Allergy, 34 (2004), pp. 59-64
[52]
H van der Vaart, DS Postma, W Timens, NHT ten Hacken.
Acute effects of cigarette smoke on inflammation and oxidative stress: a review.
Thorax, 59 (2004), pp. 713-721
[53]
JEM Tomlinson, AD McMahon, R Chaudhuri, JM Thompson, SF Wood, NC Thomson.
Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma.
Thorax, 60 (2005), pp. 282-287
[54]
NC Thomson, M Spears.
The influence of smoking on the treatment response in patients with asthma.
Curr Opin Allergy Clin Immunol, 5 (2005), pp. 57-63
[55]
PJ Barnes.
Corticosteroids: the drugs to beat.
Eur J Pharmacol, 533 (2006), pp. 2-14
[56]
B Harrison, P Stephenson, G Mohan, S Nasser.
An ongoing confidential enquiry into asthma deaths in the Eastern region of the UK, 2001-2003.
Prim Care Respir J, 14 (2005), pp. 303-313
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