New Insights Into the Epidemiology of Bronchiectasis

FOR RELATED ARTICLE, SEE PAGE 1311Bronchiectasis is more common than previously thought in the United States. The characteristics of patients with the disease in the elderly US population show a large degree of overlap with COPD and asthma.1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar These are the headline results from one of the most comprehensive studies into the epidemiology of bronchiectasis published by Henkle et al1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar in this issue of CHEST. Digging deeper reveals fascinating insights into the bronchiectasis population in the United States and beyond. FOR RELATED ARTICLE, SEE PAGE 1311 Bronchiectasis affects patients from early childhood to patients who are very elderly, but the average age in US, European, and Australasian cohorts is between 60 and 70 years with prevalence increasing markedly with age.1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 2Quint J.K. Millett E.R. Joshi M. et al.Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.Eur Respir J. 2016; 47: 186-193Crossref PubMed Scopus (306) Google Scholar, 3Aksamit T.R. O’Donnell A.E. Barker A. et al.Adult patients with bronchiectasis: a first look at the US bronchiectasis research registry.Chest. 2017; 151: 982-992Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar The analysis of Henkle et al1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar used a Medicare database and therefore focused on patients > 65 years of age, the age group in which the greatest burden of disease appears to be present in Western countries.3Aksamit T.R. O’Donnell A.E. Barker A. et al.Adult patients with bronchiectasis: a first look at the US bronchiectasis research registry.Chest. 2017; 151: 982-992Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar The first observation is around the prevalence of bronchiectasis. To estimate this, the authors used a relatively conservative definition of bronchiectasis requiring a diagnosis of bronchiectasis from a pulmonologist—identifying 252,043 patients but excluding a further approximate 320,000 patients who had a diagnosis of bronchiectasis not coming from a pulmonologist. The average prevalence during the study period was therefore 701 per 100,000 patients, making bronchiectasis a relatively common disease in this population.1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar This is not the highest prevalence so far reported because Quint et al2Quint J.K. Millett E.R. Joshi M. et al.Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.Eur Respir J. 2016; 47: 186-193Crossref PubMed Scopus (306) Google Scholar reported a prevalence of 1,200 per 100,000 persons in the same age group over the same time period in the United Kingdom, but Quint et al2Quint J.K. Millett E.R. Joshi M. et al.Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.Eur Respir J. 2016; 47: 186-193Crossref PubMed Scopus (306) Google Scholar also used a broader definition requiring a read code for bronchiectasis but not requiring a diagnosis by a pulmonologist. Using such broad diagnostic criteria would more than double the estimate of prevalence reported by Henkle et al, making the prevalence using an equivalent definition the highest ever reported. The reported prevalence in the United States for patients > 75 years of age between 1999 and 2001 was 271 per 100,000 persons, highlighting the marked increase in such estimates over time.2Quint J.K. Millett E.R. Joshi M. et al.Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.Eur Respir J. 2016; 47: 186-193Crossref PubMed Scopus (306) Google Scholar In keeping with the earlier work by Quint et al,2Quint J.K. Millett E.R. Joshi M. et al.Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.Eur Respir J. 2016; 47: 186-193Crossref PubMed Scopus (306) Google Scholar where 42% of patients with bronchiectasis had a codiagnosis of asthma and 36% had COPD, Henkle et al1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar have found 51% of their US cohort with a codiagnosis of COPD and 28.3% with a codiagnosis of asthma. The defining features of these diseases (bronchial dilatation, fixed airflow obstruction, and bronchial hyperresponsiveness) can clearly coexist in the same patient, and some have referred to patients with multiple features as having an overlap syndrome.4De Soyza A. McDonnell M.J. Goeminne P.C. et al.Bronchiectasis rheumatoid overlap syndrome is an independent risk factor for mortality in patients with bronchiectasis: a multicenter cohort study.Chest. 2017; 151: 1247-1254Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Patients with features of both diseases may have a poorer survival, but the relationships between the different airway diseases are complex.4De Soyza A. McDonnell M.J. Goeminne P.C. et al.Bronchiectasis rheumatoid overlap syndrome is an independent risk factor for mortality in patients with bronchiectasis: a multicenter cohort study.Chest. 2017; 151: 1247-1254Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 5Goeminne P.C. De Soyza A. Bronchiectasis: How to be an orphan with many parents?.Eur Respir J. 2016; 47: 10-13Crossref PubMed Scopus (36) Google Scholar, 6Mao B. Yang J.W. Lu H.W. Xu J.F. Asthma and bronchiectasis exacerbation.Eur Respir J. 2016; 47: 1680-1686Crossref PubMed Scopus (64) Google Scholar COPD and asthma are often misdiagnosed and, because of the overlapping symptomatology, patients with bronchiectasis are particularly at risk of misdiagnosis. This is hinted at in the data of Henkle et al, where only 46% of patients with a diagnostic code of bronchiectasis and COPD have a smoking history. Fixed airflow obstruction is a feature of severe bronchiectasis and arises independently of smoking and occupational exposures of other traditional COPD risk factors.7McDonnell M.J. Aliberti S. Goeminne P.C. et al.Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.Thorax. 2016; 71: 1110-1118Crossref PubMed Scopus (114) Google Scholar, 8Chalmers J.D. Chotirmall S.H. Bronchiectasis: new therapies and new perspectives.Lancet Respir Med. 2018; 6: 715-726Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar In the absence of exposures associated with COPD, I would argue it is unhelpful to refer to nonsmokers with bronchiectasis and airflow obstruction as having coexisting COPD. Instead, airflow obstruction is better seen as one of many treatable traits of bronchiectasis, avoiding the confusing language of overlap syndromes wherever possible.8Chalmers J.D. Chotirmall S.H. Bronchiectasis: new therapies and new perspectives.Lancet Respir Med. 2018; 6: 715-726Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar One of the defining features of bronchiectasis is chronic airway infection that is usually associated with recurrent respiratory tract infections requiring treatment with antibiotics.9Chalmers J.D. Aliberti S. Filonenko A. et al.Characterization of the “frequent exacerbator phenotype” in bronchiectasis.Am J Respir Crit Care Med. 2018; 197: 1410-1420Crossref PubMed Scopus (154) Google Scholar The mean frequency of exacerbations in cohorts of patients from specialist clinics is between 1 and 3 per year.9Chalmers J.D. Aliberti S. Filonenko A. et al.Characterization of the “frequent exacerbator phenotype” in bronchiectasis.Am J Respir Crit Care Med. 2018; 197: 1410-1420Crossref PubMed Scopus (154) Google Scholar In contrast in the Medicare dataset, more than one-half of the cohort did not have any exacerbations in the year prior to the study. It is therefore quite likely that the patients reported in tertiary referral centers and specialist clinics and which contribute to most published evidence on bronchiectasis are more likely to be frequent exacerbators than the bronchiectasis population at large. It is important, however, to remember that exacerbations are only one feature of bronchiectasis, and the absence of exacerbation does not equate to these patients being asymptomatic. In a survey of 711 European patients with bronchiectasis, cough with sputum production was rated as the most troublesome symptom by most patients.10Aliberti S. Masefield S. Polverino E. et al.Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration.Eur Respir J. 2016; 48: 632-647Crossref PubMed Scopus (147) Google Scholar Exacerbations have the greatest impact on long-term outcomes in bronchiectasis; therefore, we are right to be focusing energies and funding on identifying treatments that can reduce exacerbations.11De Soyza A. Aksamit T. Bandel T.J. et al.RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.Eur Respir J. 2018; 51 (pii: 1702052)Crossref Scopus (134) Google Scholar, 12Aksamit T. De Soyza A. Bandel T.J. et al.RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.Eur Respir J. 2018; 51 (pii: 1702053.)Crossref Google Scholar Nevertheless, the work of Henkle et al serves as a timely reminder that a large proportion of patients suffer with other symptoms such as cough, fatigue, sputum, weight loss, and hemoptysis. Treatments to target these traits are also urgently needed. Finally, in recent years, nontuberculous mycobacterial infection (NTM) has emerged as a key etiology of bronchiectasis in North America. Of patients overall in the US bronchiectasis registry, 63% had NTM, suggesting that NTM may be dominant etiology in the United States.3Aksamit T.R. O’Donnell A.E. Barker A. et al.Adult patients with bronchiectasis: a first look at the US bronchiectasis research registry.Chest. 2017; 151: 982-992Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar The work of Henkle et al suggests otherwise with only 1.9% of patients with newly diagnosed bronchiectasis having NTM. Although the authors rightly point out that medical records or claims data are likely to underestimate the prevalence of NTM infection, they used a robust method of trying to detect these cases by requiring either a diagnostic code for NTM (031.xx) or a prescription for at least two antibiotics used to treat NTM, such as rifamycin, ethambutol, and a macrolide.1Henkle E. Chan B. Curtis J.R. Aksamit T.R. Daley C.L. Winthrop K.L. Characteristics and health-care utilization history of patients with bronchiectasis in US Medicare enrollees with prescription drug plans, 2006 to 2014.Chest. 2018; 154: 1311-1320Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar It would therefore be anticipated that any patient being actively treated with Mycobacterium avium, for example, with guideline concordant treatment would have been detected. It therefore seems likely the true rates of NTM infection in US patients with bronchiectasis are higher than reported here, but will be much lower than the 63% reported by the US bronchiectasis registry. Rates of NTM infection of between 1% and 10% of patients have been reported in Europe, leading to a widespread view that US patients have different characteristics to European patients with a higher prevalence of NTM. Despite its limitations, the study by Henkle et al raises the possibility that this transatlantic difference may not truly exist or may be much less striking than previously thought. NTM infection is neglected in clinical practice and nonspecialists who are caring for patients with bronchiectasis may not test for NTM either at diagnosis or during follow-up. The true prevalence of NTM in bronchiectasis outside of specialist tertiary centers has therefore not been clearly established. Large-scale screening studies in bronchiectasis using standardized methods, preferably including molecular detection, should be considered to answer this question. In summary, the epidemiology of bronchiectasis has changed considerably in the last 15 years with a marked increase in prevalence. The study clearly suggests that the United States has among the highest prevalence worldwide. Routine datasets such as those reported in this study provide important insights into bronchiectasis in the real world and suggest a number of gaps persist in our understanding of this complex disease. /cms/asset/d80d4bce-1b3a-4185-9c1b-ff58009ebb27/mmc1.mp3Loading ... Download .mp3 (27.95 MB) Help with .mp3 files Audio Characteristics and Health-care Utilization History of Patients With Bronchiectasis in US Medicare Enrollees With Prescription Drug Plans, 2006 to 2014CHESTVol. 154Issue 6PreviewBronchiectasis is an increasingly common chronic inflammatory airway disease. There is an urgent need to understand the epidemiology of bronchiectasis in older adults. We describe the prevalence and characteristics of patients with bronchiectasis within the US Medicare population. Full-Text PDF ResponseCHESTVol. 155Issue 6PreviewI thank Dr Reich for raising the interesting “chicken or egg” question of whether nontuberculous mycobacterial infection (NTM) is a cause or consequence of bronchiectasis.1 It is clear that nontuberculous mycobacteria are opportunistic pathogens that are able to cause disease in patients with impaired mucociliary clearance or host defense. When patients present for the first time, it is often difficult to ascertain whether the NTM has complicated existing structural bronchiectasis or whether the NTM itself has provoked an inflammatory response leading to the development or progression of bronchiectasis. Full-Text PDF Non-TB Mycobacterial Infection-Bronchiectasis NexusCHESTVol. 155Issue 6PreviewIn the December 2018 issue of CHEST, Chalmers1 asserts, “in recent years, nontuberculous mycobacterial infection (NTM) has emerged as a key etiology of bronchiectasis in North America.” More likely, NTM by these low virulence organisms is the opportunistic consequence of a predisposing pulmonary disease (PDPD). Mycobacterium avium complex, the most frequent NTM associated with bronchiectasis, is a congeries of saprophytic, free-living, soil- and water-dwelling bacteria, frequently present in municipal water supplies where it can be aerosolized. Full-Text PDF