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class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Non-Pharmacological Interventions During SARS-CoV-2 Pandemic: Effects on Pediatric Viral Respiratory Infections" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "612" "paginaFinal" => "618" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 886 "Ancho" => 1295 "Tamanyo" => 198218 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Georgina Armero, Carmina Guitart, Aleix Soler-Garcia, Maria Melé, Cristina Esteva, Pedro Brotons, Carmen Muñoz-Almagro, Iolanda Jordan, Cristian Launes" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Georgina" "apellidos" => "Armero" ] 1 => array:2 [ "nombre" => "Carmina" "apellidos" => "Guitart" ] 2 => array:2 [ "nombre" => "Aleix" "apellidos" => "Soler-Garcia" ] 3 => array:2 [ "nombre" => "Maria" "apellidos" => "Melé" ] 4 => array:2 [ "nombre" => "Cristina" "apellidos" => "Esteva" ] 5 => array:2 [ "nombre" => "Pedro" "apellidos" => "Brotons" ] 6 => array:2 [ "nombre" => "Carmen" "apellidos" => "Muñoz-Almagro" ] 7 => array:2 [ "nombre" => "Iolanda" "apellidos" => "Jordan" ] 8 => array:2 [ "nombre" => "Cristian" "apellidos" => "Launes" ] ] ] ] "resumen" => array:2 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0015"></elsevierMultimedia></p></span>" ] 1 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0005" class="elsevierStylePara elsevierViewall">The SARS-CoV-2 pandemic provided an opportunity to assess the impact of non-pharmacological measures.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0010" class="elsevierStylePara elsevierViewall">This assessment should encompass the effects of implementing and lifting these measures.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0015" class="elsevierStylePara elsevierViewall">In this study, deseasonalized time-series analysis was used to evaluate these effects.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0020" class="elsevierStylePara elsevierViewall">The rates of rhinovirus, RSV, HMPV, and influenza detections were influenced by decisions regarding these measures.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall">Specifically, mandatory face masks for the population aged 6 and older interfered with the circulation of these viruses.</p></li></ul></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624001832?idApp=UINPBA00003Z" "url" => "/03002896/0000006000000010/v1_202410020659/S0300289624001832/v1_202410020659/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289624002369" "issn" => "03002896" "doi" => "10.1016/j.arbres.2024.06.014" "estado" => "S300" "fechaPublicacion" => "2024-10-01" "aid" => "3609" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "edi" "cita" => "Arch Bronconeumol. 2024;60:607-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "How to Protect Radon Exposed Workers? Advocating for a Specific Health Surveillance Protocol" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "607" "paginaFinal" => "608" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lucía Martín-Gisbert, Montserrat García Gómez, Alberto Ruano Ravina" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Lucía" "apellidos" => "Martín-Gisbert" ] 1 => array:2 [ "nombre" => "Montserrat" "apellidos" => "García Gómez" ] 2 => array:2 [ "nombre" => "Alberto" "apellidos" => "Ruano Ravina" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624002369?idApp=UINPBA00003Z" "url" => "/03002896/0000006000000010/v1_202410020659/S0300289624002369/v1_202410020659/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Non-Tuberculous Mycobacterial Pulmonary Disease—Where are we Now?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "609" "paginaFinal" => "611" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kartik Kumar, Michael R. Loebinger" "autores" => array:2 [ 0 => array:3 [ "nombre" => "Kartik" "apellidos" => "Kumar" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "Michael R." "apellidos" => "Loebinger" "email" => array:1 [ 0 => "m.loebinger@rbht.nhs.uk" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Host Defence Unit, Department of Respiratory Medicine, Royal Brompton Hospital, Guy's and St Thomas’ NHS Foundation Trust, London, UK" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "National Heart and Lung Institute, Imperial College London, London, UK" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Non-tuberculous mycobacteria (NTM) comprise all mycobacteria other than those that cause tuberculosis or leprosy. While several NTM species may cause significant disease, those comprising the <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">avium</span> complex (MAC) and the subspecies of <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">abscessus</span> (MAB) are among the most common encountered clinically. The lungs are the commonest site of NTM infection. There remains a poor evidence base in NTM pulmonary disease (NTM-PD) with knowledge gaps in relation to epidemiology, infection control, pathogenesis heterogeneity and optimal treatment regimens. Interest is however increasing among academics, clinicians and industry alike, with an increase in publications and clinical trial development. In this editorial, we consider some of the latest data pertaining to the epidemiology, diagnosis and management of NTM-PD.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The number of NTM infection cases continues to rise globally. In a systematic review and meta-analysis of 47 studies from over 18 countries encompassing 285,681 positive NTM isolates, 81% of the studies identified increasing trends, with a +4.0% annual rate of change for NTM infection and disease per 100,000 persons/year.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Increasing prevalence and incidence have been reported in studies from Africa, Asia, Europe, North America, South America and Oceania, with variation depending on the NTM species and MAC being the most common species in most regions.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> It should however be noted that NTM infections are not notifiable in most countries and the annual prevalence of NTM-PD may be stable in some areas.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">While several studies have investigated putative transmission of MAB clones between cohorts with cystic fibrosis (CF), less has been published on the potential transmission of other NTM species between individuals with CF, non-CF bronchiectasis or other chronic respiratory disease. Through whole genome sequencing of longitudinal sputum MAC isolates collected from a cohort in a tertiary NTM treatment centre in London, van Tonder et al. demonstrated the presence of putative transmission clusters for <span class="elsevierStyleItalic">M. avium</span> subsp. <span class="elsevierStyleItalic">avium</span>, <span class="elsevierStyleItalic">M.</span><span class="elsevierStyleItalic">avium</span> subsp. <span class="elsevierStyleItalic">hominissuis</span>, <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">intracellulare</span> and <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">chimaera</span>.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> Epidemiological links however were not identified for most individuals within the clusters and the absence of environmental sampling meant that transmission dynamics could not be fully elucidated. In another study investigating the potential transmission of MAC in a CF centre in Vermont, Gross et al. found that there was no significant genetic similarity between environmental and respiratory MAC isolates; but there was some similarity between respiratory <span class="elsevierStyleItalic">M</span>. <span class="elsevierStyleItalic">chimaera</span> isolates and those found in a hospital water biofilm sample.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a> This reinforces the notion that healthcare settings may possibly provide a reservoir for environmental acquisition of NTM; but direct human-to-human transmission has not been unequivocally proven.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Diagnosing NTM-PD is contingent upon microbiological, radiological and clinical criteria being satisfied. Danho et al. found that time-to-positivity (TTP) in Mycobacterium Growth Indicator Tube automated broth culture may predict culture conversion. A TTP of >7 days at baseline and >15 days at 3 months was predictive of culture conversion at 6 months in a cohort treated for MAC-PD.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> Culture-based techniques for mycobacteria can be slow in providing final results, causing delays in clinical decision-making. To address this, Ellis et al. developed molecular assays to quantify the burden of six NTM species. They demonstrated that a custom qPCR assay for <span class="elsevierStyleItalic">M.</span><span class="elsevierStyleItalic">abscessus</span> in particular had a high sensitivity and specificity when applied to NTM DNA extracted from longitudinally acquired sputum samples from individuals with NTM-PD; and that there was a significant decrease in mycobacterial burden associated with the use of NTM-PD treatment.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">7</span></a> Such molecular tests may hold potential utility in monitoring response to treatment in future.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Treatment regimens for NTM-PD are complex due to the use of multiple drugs, medication interactions, side effects and <span class="elsevierStyleItalic">in vitro</span> drug susceptibility testing results for NTM isolates not necessarily correlating with <span class="elsevierStyleItalic">in vivo</span> effectiveness. The use of amikacin liposome inhalation suspension (ALIS) has been extensively investigated in treatment-refractory MAC pulmonary disease (MAC-PD). In the CONVERT study, Griffith et al. demonstrated that adding ALIS to guideline-based therapy (GBT) for refractory MAC-PD resulted in improved rates of culture conversion at six months.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> Winthrop et al. subsequently showed that culture conversion continued beyond six months when using ALIS with GBT and that the most frequent adverse effects associated with treatment were respiratory in nature.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">9</span></a> Additionally, culture conversion is sustained when using ALIS with GBT for 12 months following initial conversion.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> More recently, Siegel et al. have investigated the utility of adding ALIS to multidrug regimens used in MAB pulmonary disease (MAB-PD). In a MAB-PD cohort in which all pretreatment isolates were susceptible to amikacin but most were macrolide-resistant, 6/33 individuals developed amikacin resistance following the addition of ALIS, potentially due to insufficient companion drugs.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Among the 15 participants for whom longitudinal culture data demonstrated culture conversion, 10 individuals had sustained culture conversion at 12 months.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> In view of the generally poor clinical outcomes associated with MAB-PD, these findings are noteworthy and suggest that larger scale prospective trials are warranted.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Various novel treatments have been under evaluation for the treatment of NTM-PD. Omadacycline, an aminomethylcycline, has shown potential efficacy when used in multidrug treatment regimens for MAB. In a retrospective analysis of 117 patients treated with omadacycline for MAB infections, Mingora et al. found that 44/95 (46%) of the cohort with MAB-PD had at least one negative culture at the end of the period of microbiological assessment; 17/95 (18%) met the definition for culture conversion.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> Furthermore, among those with refractory MAB-PD, 7/31 (23%) culture converted at the end of the assessment period.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> Notable side effects that limited the duration of treatment included the development of haematological abnormalities (anaemia, thrombocytopaenia, leukopaenia, eosinophilia) or liver function test derangement (transaminitis, hyperbilirubinaemia), although none of these were deemed to be life-threatening.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> Additionally, the potential utility of clofazimine in treating MAC-PD is increasingly recognised. Zweijpfenning et al. recently demonstrated that using clofazimine in place of rifampicin alongside ethambutol and a macrolide in MAC-PD resulted in similar degrees of sputum culture conversion.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Furthermore, inhaled granulocyte–macrophage colony stimulating factor has been evaluated in 24 individuals with refractory MAC-PD and 8 individuals with MAB-PD. Thomson et al. found that inhaled molgramostim in addition to GBT was associated with culture conversion in 7/24 (29.2%) MAC-PD cases and 1/8 (12.5%) MAB-PD cases with no significant safety signal.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> Inhaled nitric oxide (iNO) therapy may also show some promise. In a study of adults with NTM-PD, 4/10 (40%) of participants had negative mycobacterial sputum cultures after addition of iNO treatment; of these, three participants reverted to culture positivity three months following iNO cessation.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> Another emerging therapeutic option for NTM-PD is the use of bacteriophage therapy. In a study of 20 individuals with treatment-refractory pulmonary, extrapulmonary or disseminated mycobacterial infections who were treated with phages on compassionate grounds, at least half of the cohort subsequently had positive clinical outcomes and no adverse reactions were reported.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a> Other agents under investigation in phase 1–3 trials include epetraborole and SPR720 (a novel bacterial DNA gyrase inhibitor).<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There remain a number of unanswered questions with respect to the long-term clinical trajectories of individuals who have been treated for NTM-PD. Factors predisposing individuals to relapse or reinfection require further exploration. This should be with a view to elucidating biomarkers that can be used clinically to identify those at greatest risk of future NTM infection recurrence. Furthermore, the association between NTM and other infections should be evaluated. There is known to be a link between NTM and concomitant or sequential fungal pulmonary infection, but the mechanisms underlying this association and the appropriate strategies for monitoring and treatment are still to be determined.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">18</span></a> The value of multidisciplinary clinical management, particularly in relation to airway clearance, pulmonary rehabilitation and nutritional support, must also be remembered.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> Additionally, long-term morbidity associated with treated NTM-PD, such as the lasting impact on lung function, psychological outcomes and quality of life, merit study. The creation of validated patient-reported outcome measures is vital if this is to be achieved.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">KK prepared the original draft. MRL critically revised the manuscript for content. Both authors approved the version of the article that was submitted for publication.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interests</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">KK:</span> None declared in relation to this article.</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">MRL:</span> MRL has received honoraria for consultancy or lectures not related to this article from Insmed, Armata, 30T, Astra Zeneca, Parion, Chiesi, Zambon, Electromed, Recode, Boehringer Ingelheim, Ethris, Mannkind, AN2 Therapeutics and Cepheid.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interests" ] 3 => array:2 [ "identificador" => "xack778787" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0100" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.N. 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