Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuro... more Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene.
Therapeutic Advances in Chronic Disease, Apr 27, 2015
, using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citati... more , using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citation reference lists were reviewed to identify other relevant reports. Pertinent MDR-TB treatment reports on the US Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and Cochrane websites were also evaluated. Individuals infected with drug-sensitive (DS) MTB strains can expect excellent outcomes if they are treated according to WHO guidelines [WHO, 2010b]. Treatment defaults occur for various
Communications for this section will be published as space and priorities permit. The comments sh... more Communications for this section will be published as space and priorities permit. The comments should not exceed 350 words in length, with a nutximwn of five ref erences; onefigure or table can be printed. Exceptions may occur under particular circumstances. Contributions may include comm.ents on articles published in this periodical, or they may be reports of unique educational character.
BACKGROUND In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) ad... more BACKGROUND In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex (MAC) lung disease (ALIS+GBT, 29% [65/224] vs GBT-alone, 8.9% [10/112], P<.0001). RESEARCH QUESTION In patients who had culture conversion by month 6 in CONVERT, was conversion sustained (negative sputum cultures for 12 months on treatment) and durable (negative sputum culture for 3 months off treatment), and were there any additional safety signals associated with a full treatment course of 12 months post-conversion? STUDY DESIGN AND METHODS Adults were randomized 2:1 to receive ALIS+GBT or GBT-alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS More patients randomized to ALIS+GBT (intention-to-treat) had conversion that was both sustained and durable 3 months off treatment vs patients randomized to GBT-alone (ALIS+GBT, 16.1% [36/224] vs GBT-alone, 0% [0/112], P<.0001). Of the patients who had culture conversion by month 6, 55.4% of converters (36/65) in the ALIS+GBT-treated arm vs no converters (0/10) in the GBT-alone arm had sustained and durable conversion (P=.0017). Relapse rates through 3 months off treatment were 9.2% (6/65) in the ALIS+GBT and 30.0% (3/10) in the GBT-alone arm. Common adverse events among ALIS+GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) mainly occurred within the first 8 months of treatment. INTERPRETATION In a refractory population, conversion was sustained and durable in more patients treated with ALIS+GBT for 12 months postconversion than in those treated with GBT-alone. No new safety signals were associated with 12 months of postconversion treatment.
NTM disease is increasing in prevalence. The lung microbiome represents an ecological niche of dy... more NTM disease is increasing in prevalence. The lung microbiome represents an ecological niche of dynamic interplay unique to each individual and plays a potential role in NTM disease.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater ... more Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-gamma pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal alpha(1)-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.
; on behalf of the CHEST Expert Cough Panel * BACKGROUND: Asthma and non-asthmatic eosinophilic b... more ; on behalf of the CHEST Expert Cough Panel * BACKGROUND: Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of noninvasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB. METHODS: We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology. RESULTS: Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism. CONCLUSIONS: This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research.
BACKGROUND: Chronic cough in interstitial lung disease (ILD) causes significant impairment in qua... more BACKGROUND: Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. METHODS: This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough $ 8 weeks' duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. RESULTS: Eight randomized controlled trials and two case series ($ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma-related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma-associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. CONCLUSIONS: The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed.
BackgroundCough symptom severity represents an important subjective end-point to assess the impac... more BackgroundCough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity.ObjectiveThe aim of this study was to establish items and domains that would inform development of a new cough severity instrument.MethodsThree focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity.ResultsThe patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, ...
BACKGROUND: Cough is one of the most common presenting symptoms to general practitioners. The obj... more BACKGROUND: Cough is one of the most common presenting symptoms to general practitioners. The objective of this article is to collate the pediatric components of the CHEST chronic cough guidelines that have recently updated the 2006 guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough. METHODS: We reviewed all current CHEST Expert Cough Panel's statements and extracted recommendations and suggestions relating to children aged # 14 years with chronic cough (> 4 weeks duration). Additionally, we undertook systematic reviews to update other sections we considered relevant and important. RESULTS: The eight recent CHEST guidelines relevant to children, based on systematic reviews, reported some high-quality evidence in the management of chronic cough in children (eg, use of algorithms and management of wet/productive cough using appropriate antibiotics). However, much evidence is still inadequate, particularly in the management of nonspecific cough in the community. CONCLUSIONS: The recommendations and suggestions related to the management of chronic cough in the pediatric age group have been based upon high-quality systematic reviews and are summarized in this article. Compared to the 2006 Cough Guidelines, there is now highquality evidence for some aspects of the management of chronic cough in children. However, further studies particularly in primary health care are required.
Choosing the most appropriate antibiotic for the treatment of common infections is becoming incre... more Choosing the most appropriate antibiotic for the treatment of common infections is becoming increasingly complex. New drugs and new classes of antibiotics are being developed and made available, and emerging resistance and pharmacoeconomics play important roles. The Canadian healthcare system presents a unique challenge for prescribing physicians because pharmacoeconomic considerations are becoming increasingly important. It is important that Canadian guidelines be developed to address the needs of Canadian physicians. A consensus conference was held in October 1996 to discuss appropriate guidelines for antibiotic recommendations for common adult respiratory, urinary tract and diabetic foot infections. In August 1997, the guidelines were reviewed and updated as part of a second meeting of the group on antimicrobial resistance. The final recommendations constitute the information in this document. The panel of physicians and pharmaceutical doctors from the Prairie provinces of Albert...
BACKGROUND: In response to occupational and environmental exposures, cough can be an isolated sym... more BACKGROUND: In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected. METHODS: MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel. RESULTS: The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature. CONCLUSIONS: Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.
Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuro... more Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene.
Therapeutic Advances in Chronic Disease, Apr 27, 2015
, using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citati... more , using the terms bedaquiline, TMC 207 and R207910 identified pertinent English citations. Citation reference lists were reviewed to identify other relevant reports. Pertinent MDR-TB treatment reports on the US Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and Cochrane websites were also evaluated. Individuals infected with drug-sensitive (DS) MTB strains can expect excellent outcomes if they are treated according to WHO guidelines [WHO, 2010b]. Treatment defaults occur for various
Communications for this section will be published as space and priorities permit. The comments sh... more Communications for this section will be published as space and priorities permit. The comments should not exceed 350 words in length, with a nutximwn of five ref erences; onefigure or table can be printed. Exceptions may occur under particular circumstances. Contributions may include comm.ents on articles published in this periodical, or they may be reports of unique educational character.
BACKGROUND In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) ad... more BACKGROUND In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex (MAC) lung disease (ALIS+GBT, 29% [65/224] vs GBT-alone, 8.9% [10/112], P<.0001). RESEARCH QUESTION In patients who had culture conversion by month 6 in CONVERT, was conversion sustained (negative sputum cultures for 12 months on treatment) and durable (negative sputum culture for 3 months off treatment), and were there any additional safety signals associated with a full treatment course of 12 months post-conversion? STUDY DESIGN AND METHODS Adults were randomized 2:1 to receive ALIS+GBT or GBT-alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS More patients randomized to ALIS+GBT (intention-to-treat) had conversion that was both sustained and durable 3 months off treatment vs patients randomized to GBT-alone (ALIS+GBT, 16.1% [36/224] vs GBT-alone, 0% [0/112], P<.0001). Of the patients who had culture conversion by month 6, 55.4% of converters (36/65) in the ALIS+GBT-treated arm vs no converters (0/10) in the GBT-alone arm had sustained and durable conversion (P=.0017). Relapse rates through 3 months off treatment were 9.2% (6/65) in the ALIS+GBT and 30.0% (3/10) in the GBT-alone arm. Common adverse events among ALIS+GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) mainly occurred within the first 8 months of treatment. INTERPRETATION In a refractory population, conversion was sustained and durable in more patients treated with ALIS+GBT for 12 months postconversion than in those treated with GBT-alone. No new safety signals were associated with 12 months of postconversion treatment.
NTM disease is increasing in prevalence. The lung microbiome represents an ecological niche of dy... more NTM disease is increasing in prevalence. The lung microbiome represents an ecological niche of dynamic interplay unique to each individual and plays a potential role in NTM disease.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater ... more Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-gamma pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal alpha(1)-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.
; on behalf of the CHEST Expert Cough Panel * BACKGROUND: Asthma and non-asthmatic eosinophilic b... more ; on behalf of the CHEST Expert Cough Panel * BACKGROUND: Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of noninvasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB. METHODS: We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology. RESULTS: Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism. CONCLUSIONS: This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research.
BACKGROUND: Chronic cough in interstitial lung disease (ILD) causes significant impairment in qua... more BACKGROUND: Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. METHODS: This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough $ 8 weeks' duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. RESULTS: Eight randomized controlled trials and two case series ($ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma-related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma-associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. CONCLUSIONS: The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed.
BackgroundCough symptom severity represents an important subjective end-point to assess the impac... more BackgroundCough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity.ObjectiveThe aim of this study was to establish items and domains that would inform development of a new cough severity instrument.MethodsThree focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity.ResultsThe patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, ...
BACKGROUND: Cough is one of the most common presenting symptoms to general practitioners. The obj... more BACKGROUND: Cough is one of the most common presenting symptoms to general practitioners. The objective of this article is to collate the pediatric components of the CHEST chronic cough guidelines that have recently updated the 2006 guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough. METHODS: We reviewed all current CHEST Expert Cough Panel's statements and extracted recommendations and suggestions relating to children aged # 14 years with chronic cough (> 4 weeks duration). Additionally, we undertook systematic reviews to update other sections we considered relevant and important. RESULTS: The eight recent CHEST guidelines relevant to children, based on systematic reviews, reported some high-quality evidence in the management of chronic cough in children (eg, use of algorithms and management of wet/productive cough using appropriate antibiotics). However, much evidence is still inadequate, particularly in the management of nonspecific cough in the community. CONCLUSIONS: The recommendations and suggestions related to the management of chronic cough in the pediatric age group have been based upon high-quality systematic reviews and are summarized in this article. Compared to the 2006 Cough Guidelines, there is now highquality evidence for some aspects of the management of chronic cough in children. However, further studies particularly in primary health care are required.
Choosing the most appropriate antibiotic for the treatment of common infections is becoming incre... more Choosing the most appropriate antibiotic for the treatment of common infections is becoming increasingly complex. New drugs and new classes of antibiotics are being developed and made available, and emerging resistance and pharmacoeconomics play important roles. The Canadian healthcare system presents a unique challenge for prescribing physicians because pharmacoeconomic considerations are becoming increasingly important. It is important that Canadian guidelines be developed to address the needs of Canadian physicians. A consensus conference was held in October 1996 to discuss appropriate guidelines for antibiotic recommendations for common adult respiratory, urinary tract and diabetic foot infections. In August 1997, the guidelines were reviewed and updated as part of a second meeting of the group on antimicrobial resistance. The final recommendations constitute the information in this document. The panel of physicians and pharmaceutical doctors from the Prairie provinces of Albert...
BACKGROUND: In response to occupational and environmental exposures, cough can be an isolated sym... more BACKGROUND: In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected. METHODS: MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel. RESULTS: The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature. CONCLUSIONS: Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.
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