Scientific Letter
Severe Pulmonary Emphysema in a Young Patient With Vasculitis Associated with Proteinase-3 Anti-Neutrophil Cytoplasmic Antibodies (PR3-ANCA)
Enfisema pulmonar severo en un paciente joven con una vasculitis asociada a anticuerpos anticitoplasma de neutrófilo tipo proteinasa-3 (ANCA-PR3)
Salomé Muray Cases
, Concepción Alcázar Fajardo, Juan B. Cabezuelo Romero
Corresponding author
Servicio de Nefrología, Hospital General Universitario Reina Sofía, Murcia, Spain
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Cabezuelo Romero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Salomé" "apellidos" => "Muray Cases" "email" => array:1 [ 0 => "salomuray@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Concepción" "apellidos" => "Alcázar Fajardo" ] 2 => array:2 [ "nombre" => "Juan B." "apellidos" => "Cabezuelo Romero" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Nefrología, Hospital General Universitario Reina Sofía, Murcia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfisema pulmonar severo en un paciente joven con una vasculitis asociada a anticuerpos anticitoplasma de neutrófilo tipo proteinasa-3 (ANCA-PR3)" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1447 "Ancho" => 3000 "Tamanyo" => 419425 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Images of renal biopsy (A) and chest CT (B–F). (A) 2 glomeruli with extracapillary (or crescent) proliferation (periodic acid Schiff). (B–F) Different chest CT slices showing bilateral mixed centrilobular emphysema, with areas of paraseptal involvement and subpleural bullae, mainly in the upper lobes. (F) One of the nodules, measuring 3.1<span class="elsevierStyleHsp" style=""></span>mm (dotted line).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary involvement is common in ANCA-associated vasculitis (AAV), but rarely manifests as pulmonary emphysema (13% of cases).<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 32-year-old man, smoker of 13 pack-years, with no exposure to other toxic substances, no family history, and no significant clinical history, who was diagnosed with anti-proteinase 3 (PR3) c-ANCA vasculitis and severe pulmonary emphysema. At the time of diagnosis, the patient had constitutional symptoms, arthralgia, digital ischemia, and kidney diseases in the form of non-nephrotic proteinuria, and microhematuria with normal glomerular filtration. Clinical laboratory tests revealed hemoglobin 12.2<span class="elsevierStyleHsp" style=""></span>g/dl and elevated ESR and C-reactive protein. The immunological study was positive for c-ANCA, with an anti-PR3 titer of 79<span class="elsevierStyleHsp" style=""></span>U/ml (normal value <2<span class="elsevierStyleHsp" style=""></span>U/ml) and anti-MPO 0<span class="elsevierStyleHsp" style=""></span>U/ml. Other studies, which included anti-glomerular basement membrane antibodies, ANA, complement, immunoglobulins, cryoglobulins, antiphospholipid antibodies, proteinogram, and hepatitis B, C, and HIV serologies, were normal or negative. Mantoux and Quantiferon<span class="elsevierStyleSup">®</span> were negative. Kidney biopsy showed pauci-immune extracapillary proliferative glomerulonephritis with crescent formation in 46% of the glomeruli (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). ENT computed tomography revealed no significant changes; chest CT showed 3 nodules <5<span class="elsevierStyleHsp" style=""></span>mm in the right lung, and severe bilateral diffuse mixed centrilobular emphysema with areas of paraseptal involvement and subpleural bullae, mainly in the upper lobes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B–F). No siderophages were found in sputum. Of note on lung function tests were: DLCO: 68%; KCO: 66%; FEF 25%–75%: 58%; FEV1: 80%; and FEV1/FVC: 69%. He was treated with glucocorticoids at a starting dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day p.o. in a tapering schedule, and intravenous cyclophosphamide according to the CYCLOPS scheme.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> The patient stopped smoking and began treatment with bronchodilators. Alpha-1 antitrypsin levels were determined twice, and were normal on both occasions (140 and 145<span class="elsevierStyleHsp" style=""></span>mg/dl, respectively). PI*S and Pi*Z alleles of the AAT gene were also determined qualitatively using PCR-ARMS and were negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Six months later, after completing induction therapy, the patient achieved clinical remission and began treatment with azathioprine. Respiratory problems included several infections that were managed with oral antibiotics. No significant changes were found on chest CT, and the 3 nodules previously visualized remained stable. Lung tests performed at that time showed DLCO: 46%; KCO: 60%; FEF 25%–75%: 65%; FEV1: 78%; and FEV1/FVC: 76%.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Cases of pulmonary emphysema, some associated with AAT deficiency (AATD), have been reported in patients with AAV.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a> One clear cause of our patient's pulmonary emphysema was his smoking habit.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> In general, accumulated tobacco consumption correlates with the severity of the lung disease. In the absence of other genetic and/or environmental factors, it is thought very unlikely that lung disease will develop with an exposure of less than 10–15 pack-years, and the only clearly associated factor is a habit of over 40 pack-years.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">4,5</span></a> In our patient, the severity of the emphysema, his age, and tobacco exposure below the limits mentioned above led us to consider other possible causes (such as other toxic substances, and particularly AATD and a deficient genetic allele). However, the contribution of AAV to his pulmonary emphysema cannot be ruled out, and this factor may also explain the deterioration of KCO, despite giving up smoking. The pathogenic link between these 2 factors is not well established. In our case, no clinical evidence of previous diffuse alveolar hemorrhage that might have resulted in emphysema was observed. AAT is an inhibitor of serine proteases, including elastase and PR3, that are found in primary neutrophil granules and are involved in tissue breakdown.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> Tobacco use increases pulmonary levels of metalloproteinase and elastase, released by the alveolar macrophages and neutrophils, respectively, and functional inhibition of AAT.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7,8</span></a> In vasculitis, ANCA cause degranulation of neutrophils with the consequent release of proteases from their primary granules (PR3 and elastase) (respiratory burst), and also interfere in the formation of PR3-AAT complexes, preventing the neutralization of these proteases.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">9–12</span></a> Therefore, it is possible that in smokers with AAV, protease/antiprotease imbalance in the extracellular fluid results in increased destruction of elastin, a protein matrix essential for maintaining the structural integrity of the lungs, thus contributing to the severity of the pulmonary emphysema. However, the <span class="elsevierStyleItalic">in vivo</span> interaction between PR3, AAT and ANCAs still has not been definitively established. Lastly, the patient's pulmonary nodules, while possibly associated with the ANCA-PR3 vasculitis, were interpreted as nonspecific because they persisted despite remission of the vasculitis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In short, pulmonary emphysema can coexist with ANCA-associated vasculitis, and the pathogenic contribution of this process, in addition to other clearly associated factors, such as tobacco and AADT, cannot be ruled out.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Muray Cases S, Alcázar Fajardo C, Cabezuelo Romero JB. Enfisema pulmonar severo en un paciente joven con una vasculitis asociada a anticuerpos anticitoplasma de neutrófilo tipo proteinasa-3 (ANCA-PR3). Arch Bronconeumol. 2018;54:397–399</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1447 "Ancho" => 3000 "Tamanyo" => 419425 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Images of renal biopsy (A) and chest CT (B–F). (A) 2 glomeruli with extracapillary (or crescent) proliferation (periodic acid Schiff). (B–F) Different chest CT slices showing bilateral mixed centrilobular emphysema, with areas of paraseptal involvement and subpleural bullae, mainly in the upper lobes. (F) One of the nodules, measuring 3.1<span class="elsevierStyleHsp" style=""></span>mm (dotted line).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: the influence of ANCA subtype" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.J. Mohammad" 1 => "K.H. Mortensen" 2 => "J. Babar" 3 => "R. Smith" 4 => "R.B. Jones" 5 => "D. Nakagomi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.161224" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2017" "volumen" => "44" "paginaInicial" => "1458" "paginaFinal" => "1467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28765242" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0070" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Granulomatosis with polyangiitis and associated pulmonary emphysema: breathtaking vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.K. Gadre" 1 => "J.K. Stoller" 2 => "A.C. Mehta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0970-2113.159576" "Revista" => array:6 [ "tituloSerie" => "Lung India" "fecha" => "2015" "volumen" => "32" "paginaInicial" => "367" "paginaFinal" => "369" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26180387" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0075" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associate vasculitis: a randomized trial" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "EUVAS (European Vasculitis Study Group)" "etal" => true "autores" => array:6 [ 0 => "K. De Groot" 1 => "L. Herper" 2 => "D.R. Jayne" 3 => "L.F. Flores Suarez" 4 => "G. Gregorini" 5 => "W.L. Gross" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2009" "volumen" => "150" "paginaInicial" => "670" "paginaFinal" => "680" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19451574" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0080" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Qaseem" 1 => "T.J. Wilt" 2 => "S.E. Weinberger" 3 => "N.A. Hanania" 4 => "G. Criner" 5 => "T. van der Molen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-155-3-201108020-00008" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2011" "volumen" => "155" "paginaInicial" => "179" "paginaFinal" => "191" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21810710" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0085" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The rational clinical examination: evidence-based clinical diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Simel" 1 => "D. Rennie" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2008" "editorial" => "McGraw Hill" "editorialLocalizacion" => "New York" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0090" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Alpha-1-antitrypsin deficiency. Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.omim.org/entry/613490">http://www.omim.org/entry/613490</a> [accessed 02.01.18]." ] ] ] 6 => array:3 [ "identificador" => "bib0095" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute cigarette smoke-induced connective tissue breakdown requires both neutrophils and macrophage metalloelastase in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Churg" 1 => "K. Zay" 2 => "S. Shay" 3 => "C. Xie" 4 => "S.D. Shapiro" 5 => "R. Hendricks" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/rcmb.4791" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2002" "volumen" => "27" "paginaInicial" => "368" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12204900" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0100" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmunity in chronic obstructive pulmonary disease: clinical and experimental evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Kheradmand" 1 => "M. Shan" 2 => "C. Xu" 3 => "D.B. Corry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/eci.12.7" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Clin Immunol" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "285" "paginaFinal" => "292" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22390492" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0105" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha-1-antitrypsin phenotyping in ANCA-associated diseases: one of several arguments for protease/antiprotease imbalance in systemic vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V.L. Esnault" 1 => "M.A. Audrain" 2 => "R. Sesboüé" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Exp Clin Immunogenet" "fecha" => "1997" "volumen" => "14" "paginaInicial" => "206" "paginaFinal" => "213" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9493789" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0110" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.L. Esnault" 1 => "A. Testa" 2 => "M. Audrain" 3 => "C. Rogé" 4 => "M. Hamidou" 5 => "J.H. Barrier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1993" "volumen" => "43" "paginaInicial" => "1329" "paginaFinal" => "1332" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8315946" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0115" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New pathophysiological insights and treatment of ANCA-associated vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Wilde" 1 => "P. van Paassen" 2 => "O. Witzke" 3 => "J.W. Tervaert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.2010.472" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2011" "volumen" => "79" "paginaInicial" => "599" "paginaFinal" => "612" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21150876" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0120" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenesis of ANCA-associated vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Flint" 1 => "M.D. Morgan" 2 => "C.O. Savage" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rdc.2010.05.006" "Revista" => array:6 [ "tituloSerie" => "Rheum Dis Clin North Am" "fecha" => "2010" "volumen" => "36" "paginaInicial" => "463" "paginaFinal" => "477" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20688244" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005400000007/v1_201807020412/S1579212918301496/v1_201807020412/en/main.assets" "Apartado" => array:4 [ "identificador" => "49861" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005400000007/v1_201807020412/S1579212918301496/v1_201807020412/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918301496?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 2 | 13 |
| 2024 October | 87 | 34 | 121 |
| 2024 September | 81 | 28 | 109 |
| 2024 August | 93 | 43 | 136 |
| 2024 July | 77 | 30 | 107 |
| 2024 June | 76 | 30 | 106 |
| 2024 May | 96 | 34 | 130 |
| 2024 April | 69 | 41 | 110 |
| 2024 March | 47 | 29 | 76 |
| 2024 February | 32 | 22 | 54 |
| 2023 March | 12 | 4 | 16 |
| 2023 February | 76 | 30 | 106 |
| 2023 January | 55 | 37 | 92 |
| 2022 December | 62 | 36 | 98 |
| 2022 November | 53 | 34 | 87 |
| 2022 October | 78 | 54 | 132 |
| 2022 September | 50 | 33 | 83 |
| 2022 August | 78 | 58 | 136 |
| 2022 July | 58 | 55 | 113 |
| 2022 June | 65 | 43 | 108 |
| 2022 May | 63 | 45 | 108 |
| 2022 April | 76 | 35 | 111 |
| 2022 March | 77 | 46 | 123 |
| 2022 February | 77 | 71 | 148 |
| 2022 January | 67 | 47 | 114 |
| 2021 December | 55 | 50 | 105 |
| 2021 November | 73 | 52 | 125 |
| 2021 October | 103 | 61 | 164 |
| 2021 September | 82 | 55 | 137 |
| 2021 August | 59 | 44 | 103 |
| 2021 July | 46 | 33 | 79 |
| 2021 June | 47 | 44 | 91 |
| 2021 May | 40 | 42 | 82 |
| 2021 April | 125 | 102 | 227 |
| 2021 March | 65 | 53 | 118 |
| 2021 February | 54 | 29 | 83 |
| 2021 January | 39 | 27 | 66 |
| 2020 December | 47 | 22 | 69 |
| 2020 November | 71 | 37 | 108 |
| 2020 October | 56 | 40 | 96 |
| 2020 September | 51 | 30 | 81 |
| 2020 August | 49 | 29 | 78 |
| 2020 July | 42 | 27 | 69 |
| 2020 March | 30 | 7 | 37 |
| 2020 February | 43 | 13 | 56 |
| 2020 January | 45 | 14 | 59 |
| 2019 December | 50 | 10 | 60 |
| 2019 November | 50 | 15 | 65 |
| 2019 October | 59 | 19 | 78 |
| 2019 September | 39 | 9 | 48 |
| 2019 August | 39 | 20 | 59 |
| 2019 July | 34 | 19 | 53 |
| 2019 June | 41 | 9 | 50 |
| 2019 May | 52 | 17 | 69 |
| 2019 April | 42 | 24 | 66 |
| 2019 March | 44 | 16 | 60 |
| 2019 February | 37 | 25 | 62 |
| 2019 January | 36 | 21 | 57 |
| 2018 December | 1 | 2 | 3 |
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