Comparison of Profiles of First Nations and Non-First Nations Children With Bronchiectasis Over Two 5-Year Periods in the Northern Territory, Australia.

BACKGROUND: Although the burden of bronchiectasis is recognized globally, pediatric data are limited, particularly on trends over the years. Also, no published data exists regarding whether vitamin D deficiency or insufficiency and human T-cell lymphotropic virus type 1 (HTLV-1) infection, both found to be related to severe bronchiectasis in First Nations adults, also are important in children with bronchiectasis. RESEARCH QUESTION: Among children with bronchiectasis, (1) have the clinical and BAL profiles changed between two 5-year periods (period 1, 2007-2011; period 2, 2012-2016) and (b) are vitamin D deficiency or insufficiency, HTLV-1 infection, or both associated with radiologic severity of bronchiectasis? STUDY DESIGN AND METHODS: We analyzed the data from children with bronchiectasis prospectively enrolled at Royal Darwin Hospital, Australia, at the first diagnosis; that is, no child was included in both periods. Data collected include demographics, BAL, routine investigation bloods, and high-resolution CT scan of the chest evaluated using the Bhalla and modified Bhalla scores. RESULTS: The median age of the 299 children was 2.2 years (interquartile range, 1.5-3.7 years). One hundred sixty-eight (56%) were male and most were First Nations (92%). Overall, bronchiectasis was high over time, particularly among First Nations children. In the later period, numbers of non-First Nations children more than tripled, but did not reach statistical significance. In period 2 compared with period 1, fewer First Nations children demonstrated chronic cough (period 1, 61%; period 2, 47%; P = .03), and were younger, First Nations children were less likely to have received azithromycin (period 1, 42%; period 2, 21%; P < .001), and the BAL fluid of First Nations children showed lower Haemophilus influenzae and Moraxella catarrhalis infection. HTLV-1 infection was not detected, and vitamin D deficiency or insufficiency did not correlate with severity of bronchiectasis. INTERPRETATION: Bronchiectasis remains high particularly among First Nations children. Important changes in their profiles that arguably reflect improvements were present, but overall, the profiles remained similar. Although vitamin D deficiency was uncommon, its role in children with bronchiectasis requires further evaluation. HTLV-1 infection was nonexistent and is unlikely to play any role in First Nations children with bronchiectasis.

Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis.

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.

Culturally Appropriate Outreach Specialist Respiratory Medical Care Improves the Lung Function of Children in Regional and Remote Queensland.

BACKGROUND AND OBJECTIVES: Indigenous Respiratory Outreach Care (IROC) is a culturally appropriate specialist respiratory service established to deliver multidisciplinary respiratory care to regional and remote Queensland communities. Our objective was to evaluate the impact of an outreach specialist respiratory service on the spirometry of children attending IROC clinics, particularly Indigenous children with asthma and bronchiectasis. METHODS: Retrospective single-arm cohort study of 189 children who performed spirometry at twelve sites across regional and remote Queensland between October 2010 and December 2017. Each child's baseline spirometry was compared to their best spirometry at follow-up visit occurring within (1) 12 months of their most recent visit with at least 12 months of specialist care and; (2) each year of their first 3 years of care. RESULTS: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) z-scores improved significantly across the whole group from baseline to follow-up (change in z-scores (Δz) of FEV1 = 0.38, 95% CI 0.22, 0.53; ΔzFVC = 0.36, 95% CI 0.21, 0.51). In subgroup analyses, lung function significantly improved in Indigenous children (n = 141, ΔzFEV1 = 0.37, 95% CI 0.17, 0.57; ΔzFVC = 0.36, 95% CI 0.17, 0.55) including those with asthma (n = 117, ΔzFEV1 = 0.41, 95% CI 0.19, 0.64; ΔzFVC = 0.46, 95% CI 0.24, 0.68) and bronchiectasis (n = 38, ΔzFEV1 = 0.33, 95% CI 0.07, 0.59; ΔzFVC = 0.26, 95% CI - 0.03, 0.53). Significant improvements in FEV1 and FVC were observed within the first and second year of follow-up for Indigenous children, but not for non-Indigenous children. CONCLUSION: The IROC model of care in regional and remote settings leads to significant lung function improvement in Indigenous children with asthma and bronchiectasis.

Clinical course of chronic suppurative lung disease and bronchiectasis in Alaska Native children.

INTRODUCTION: Alaska Native (AN) children from the Yukon Kuskokwim (YK) Delta region have high rates of chronic suppurative lung disease (CSLD), including bronchiectasis. We characterized the clinical progress of an AN adolescent cohort with CSLD/bronchiectasis, and estimated bronchiectasis prevalence trends in this region. METHODS: The original cohort comprised 41 AN children (originally aged 0.5-8 years) with CSLD/bronchiectasis, recruited between 2005 and 2008, with follow-up in 2015-2016. Clinical assessments, lung function, radiography, medical chart review, and spirometry were obtained. We also conducted data queries of bronchiectasis diagnoses in YK individuals born between 1990 and 2010 to estimate prevalence. RESULTS: Thirty-four (83%) of the original cohort aged 7.3-17.6 years were reviewed, of whom 14 (41%) had high-resolution computed tomography (HRCT)-confirmed bronchiectasis, eight (24%) had no evidence of bronchiectasis on HRCT scans, while 12 (35%) had not undergone HRCT scans. Annual lower respiratory tract infection (LRTI) frequency decreased with age, although 27 (79%) still had respiratory symptoms, including all with HRCT-confirmed bronchiectasis, who were also more likely than those without confirmed bronchiectasis to have recent wheeze (80 vs 25%, P = 0.005), auscultatory crackles (60 vs 0%, P < 0.001), and lower mean forced expiratory volume in 1-second/forced vital capacity ratio (73 vs 79%, P = 0.03). The bronchiectasis prevalence for YK AN people born during 2000-2009 was 7 per 1000 births, which was lower than previously reported. CONCLUSION: Despite reduced LRTI frequency, most AN children with CSLD/bronchiectasis had symptoms/signs of underlying lung disease as they entered adolescence. Close clinical follow-up remains essential for managing these patients as they transition to adulthood.

Characteristics and Health-care Utilization History of Patients With Bronchiectasis in US Medicare Enrollees With Prescription Drug Plans, 2006 to 2014.

BACKGROUND: Bronchiectasis 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. METHODS: Among the 40% of Medicare enrollees with prescription drug plans from 2006 to 2014, we identified patients ≥ 65 years of age with bronchiectasis by International Classification of Diseases, Ninth Revision, Clinical Modification claims (494.0 or 494.1) from a pulmonologist and no claim for cystic fibrosis. We calculated the prevalence from 2012 to 2014. Incident or newly diagnosed patients were those enrolled in Medicare at least 12 months prior to the first bronchiectasis diagnosis. We described clinical and health-care utilization characteristics for this cohort during the prior 12-month (baseline) period, and explored differences between those with and without a COPD diagnosis. RESULTS: We identified 252,362 patients with bronchiectasis meeting all eligibility criteria. The average annual prevalence from 2012 to 2014 was 701 per 100,000 persons. Newly diagnosed patients were a mean age of 76 years, predominately women (65%), and predominately white, non-Hispanic (84%). During the baseline period, 12% were hospitalized for respiratory infections. Fifty-one percent had a dual diagnosis of COPD. Newly diagnosed patients with bronchiectasis and COPD had significantly different characteristics and utilization, for example were more likely hospitalized for respiratory infections during the baseline period (16% vs 7%) and to have a smoking history (46% vs 17%) compared with those without a dual COPD diagnosis, respectively. CONCLUSIONS: We confirmed a high prevalence of bronchiectasis in the United States and significant heterogeneity in patients with bronchiectasis with and without COPD that should be further explored.

Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians.

BACKGROUND: The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). METHODOLOGY/PRINCIPAL FINDINGS: 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). CONCLUSION/SIGNIFICANCE: Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.

Bronchiectasis in indigenous and non-indigenous residents of Australia and New Zealand.

BACKGROUND AND OBJECTIVE: Bronchiectasis not associated with cystic fibrosis is an increasingly recognized chronic lung disease. In Oceania, indigenous populations experience a disproportionately high burden of disease. We aimed to describe the natural history of bronchiectasis and identify risk factors associated with premature mortality within a cohort of Aboriginal Australians, New Zealand Maori and Pacific Islanders, and non-indigenous Australians and New Zealanders. METHODS: This was a retrospective cohort study of bronchiectasis patients aged >15 years at three hospitals: Alice Springs Hospital and Monash Medical Centre in Australia, and Middlemore Hospital in New Zealand. Data included demographics, ethnicity, sputum microbiology, radiology, spirometry, hospitalization and survival over 5 years of follow-up. RESULTS: Aboriginal Australians were significantly younger and died at a significantly younger age than other groups. Age- and sex-adjusted all-cause mortality was higher for Aboriginal Australians (hazard ratio (HR): 3.9), and respiratory-related mortality was higher for both Aboriginal Australians (HR: 4.3) and Maori and Pacific Islander people (HR: 1.7). Hospitalization was common: Aboriginal Australians had 2.9 admissions/person-year and 16.9 days in hospital/person-year. Despite Aboriginal Australians having poorer prognosis, calculation of the FACED score suggested milder disease in this group. Sputum microbiology varied with Aspergillus fumigatus more often isolated from non-indigenous patients. Airflow obstruction was common (66.9%) but not invariable. CONCLUSIONS: Bronchiectasis is not one disease. It has a significant impact on healthcare utilization and survival. Differences between populations are likely to relate to differing aetiologies and understanding the drivers of bronchiectasis in disadvantaged populations will be key.

Ethnicity, socioeconomic status and the severity and course of non-cystic fibrosis bronchiectasis.

BACKGROUND AND AIMS: This study evaluated whether there are ethnic factors which affect the severity and progression of bronchiectasis in our adult multi-ethnic population in Auckland, New Zealand. METHODS: Clinical records were reviewed from patients attending the outpatient facilities of our institution between 2007 and 2010. Data collected included demographics, clinical features, smoking status, self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and sputum microbiology. RESULTS: A total of 437 patients was identified: median age 65 years, 66% female, mean forced expiratory volume in the first second (FEV1 ) 62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared to the institution population catchment and had more severe impairment of lung function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6, Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However, no overall decline was seen in serial lung function measurements, either across the whole cohort or in any particular ethnic group. CONCLUSIONS: Patients of Maori and Pacific ethnicity are both overrepresented and have more severe bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did not predict decline in pulmonary function. Further studies into genetic predisposition to bronchiectasis in Maori or Pacific people may be warranted.

Diminished Susceptibility of African-Americans to Non-tuberculous Mycobacterial Disease.

The incidence of three granulomatous response diseases-sarcoidosis, tuberculosis, and non-tuberculous mycobacterial pulmonary disease-differ markedly in African-Americans versus Caucasians. In reviewing a large compendium of non-cystic-fibrosis bronchiectasis, we noted that complicating infection with non-tuberculous mycobacteria was relatively infrequent among individuals of African-American descent, confirming previous observations of their inherent resistance. Disease-specific variance among African-Americans in the efficacy of their granulomatous response suggests a nexus, a mediating, immunological mechanism. Environmentally conditioned selection of SLC11A1 (Nramp1) alleles may account for this ethnic variance.

Hospital admissions for non-cystic fibrosis bronchiectasis in New Zealand.

AIM: To investigate hospital admissions for non-cystic fibrosis bronchiectasis during July 1, 2008 to June 30, 2013; and to describe their distribution and annual cost in New Zealand. METHODS: Admissions with a principal diagnosis of bronchiectasis (ICD10 J47), excluding cystic fibrosis, and length of stay <90 days were analysed by age, sex, ethnicity, socioeconomic deprivation, DHB, re-admissions and seasonality. RESULTS: There were 5,494 admissions with a mean annual rate of 25.7 (age adjusted rate 20.4) per 100,000. Admission rates peaked in childhood and in the elderly, and increased steeply with socioeconomic deprivation. Age-adjusted rates were 38% higher for women, 4.9-fold higher for Maori and 9.1-fold higher for Pacific peoples. Counties Manukau had the highest unadjusted rate for any DHB (49.4 per 100,000). The overall 30 day readmission rate was 12.4%. Admissions peaked in winter and spring. The estimated cost in financial year 2012/13 was NZD 5.34M. CONCLUSION: Hospital admissions for bronchiectasis are concentrated in socioeconomically disadvantaged young and elderly Maori and Pacific peoples; are more common in winter and spring, and incur a high annual cost. Evidence-based interventions to reduce the disproportionate burden of bronchiectasis in Maori and Pacific children and the elderly is a public health priority.

High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis.

Aetiology of bronchiectasis in Guangzhou, southern China.

BACKGROUND AND OBJECTIVE: Aetiologies of bronchiectasis in mainland China and their comparisons with those in western countries are unknown. We aimed to investigate bronchiectasis aetiologies in Guangzhou, southern China, and to determine ethnic or geographic differences with reports from western countries. METHODS: Consecutive patients with steady-state bronchiectasis were randomly recruited. Past history was meticulously extracted. Patients underwent physical examination, saccharine test, humoral immunity assays, gastroesophageal reflux scoring and sputum culture. Fiberoptic bronchoscopy, total immunoglobin E (IgE) and Aspergillus fumigatus-specific IgE measurement, 24-h gastroesophageal pH monitoring and miscellaneous screening tests were performed, if indicated. This entailed comparisons on aetiologies with literature reports. RESULTS: We enrolled 148 patients (44.6 ± 13.8 years, 92 females), most of whom had mild to moderate bronchiectasis. Idiopathic (46.0%), post-infectious (27.0%) and immunodeficiency (8.8%) were the most common aetiologies. Miscellaneous aetiologies consisted of asthma (5.4%), gastroesophageal reflux (4.1%), aspergillosis (2.7%), congenital lung malformation (2.0%), Kartagener syndrome (1.4%), rheumatoid arthritis (1.4%), chronic obstructive pulmonary disease (0.7%), Young's syndrome (0.7%), yellow nail's syndrome (0.7%), eosinophilic bronchiolitis (0.7%) and foreign bodies (0.7%). No notable differences in clinical characteristics between idiopathic and known aetiologies were found. Ethnic or geographic variations of aetiologies were overall unremarkable. CONCLUSIONS: Idiopathic, post-infectious and immunodeficiency constitute major bronchiectasis aetiologies in Guangzhou. Clinical characteristics of patients between known aetiologies and idiopathic bronchiectasis were similar. Ethnicity and geography only account for limited differences in aetiologic spectra. These findings will offer rationales for early diagnosis and management of bronchiectasis in future studies and clinical practice in China.

Bronchiectasis in children from Qikiqtani (Baffin) Region, Nunavut, Canada.

RATIONALE: Bronchiectasis not related to cystic fibrosis is common in indigenous populations globally, but it has not been studied in Canadian indigenous children. OBJECTIVE: The objective of this study was to describe bronchiectasis in Canadian Inuit children and examine potentially causal factors. METHODS: We described the clinical features of bronchiectasis in Canadian Inuit children residing in the Qikiqtani (Baffin) Region, Nunavut, Canada, by performing a retrospective chart review of children from this region. Patients had computed tomography-confirmed bronchiectasis and were diagnosed at the Children's Hospital of Eastern Ontario, Ottawa, Canada, the regional tertiary center, between 1998 and 2011. MEASUREMENTS AND MAIN RESULTS: We identified 17 cases of bronchiectasis. We conservatively estimated the prevalence at 202/100,000 children. Bronchiectasis was strongly associated with lower respiratory tract infection (LRTI) in infancy. Reported environmental tobacco smoke exposure and overcrowding in the home appeared to be common. The left lower lobe was the most common lung lobe involved. Haemophilus influenza, Streptococcus, and Streptococcus pneumoniae were commonly isolated. The range of FEV1 values measured during pulmonary function testing was 46-108% predicted. CONCLUSIONS: Previous researchers have reported that Canadian Inuit children have markedly elevated rates of LRTI early in life. Our study suggests that this may lead to long-term pulmonary sequelae. Preventing LRTI in Inuit infants may both prevent acute, severe illness and reduce their risk of developing permanent lung damage.

Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis.

BACKGROUND: The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. METHODS: The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St George's Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. RESULTS: Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.

Respiratory exacerbations in indigenous children from two countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.

BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial.

BACKGROUND: Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). METHODS/DESIGN: This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. DISCUSSION: We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George's respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease. TRIAL REGISTRATION: This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013.

Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.

OBJECTIVE: Indigenous children in developed countries are at increased risk of chronic suppurative lung disease (CSLD), including bronchiectasis. We evaluated sociodemographic and medical factors in indigenous children with CSLD/bronchiectasis from Australia, United States (US), and New Zealand (NZ). METHODS: Indigenous children aged 0.5-8 years with CSLD/bronchiectasis were enrolled from specialist clinics in Australia (n = 97), Alaska (n = 41), and NZ (n = 42) during 2004-2009, and followed for 1-5 years. Research staff administered standardized parent interviews, reviewed medical histories and performed physical examinations at enrollment. RESULTS: Study children in all three countries had poor housing and sociodemographic circumstances at enrollment. Except for increased household crowding, most poverty indices in study participants were similar to those reported for their respective local indigenous populations. However, compared to their local indigenous populations, study children were more often born prematurely and had both an increased frequency and earlier onset of acute lower respiratory infections (ALRIs). Most (95%) study participants had prior ALRI hospitalizations and 77% reported a chronic cough in the past year. Significant differences (wheeze, ear disease and plumbed water) between countries were present. DISCUSSION: Indigenous children with CSLD/bronchiectasis from three developed countries experience significant disparities in poverty indices in common with their respective indigenous population; however, household crowding, prematurity and early ALRIs were more common in study children than their local indigenous population. Addressing equity, especially by preventing prematurity and ALRIs, should reduce risk of CSLD/bronchiectasis in indigenous children.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. METHODS: Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1-2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. FINDINGS: 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. INTERPRETATION: Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study. FUNDING: National Health and Medical Research Council (Australia) and Health Research Council (New Zealand).

Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. METHODS/DESIGN: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV(1); for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms. DISCUSSION: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.

Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture.

BACKGROUND: Previous studies of patients with bronchiectasis have found that the cause is idiopathic in the majority of cases, but these studies were done in homogeneous populations. We hypothesized that the etiology of bronchiectasis can be determined in a higher percentage of patients in a diverse US population and will differ significantly based on ethnicity. METHODS: One hundred twelve patients with bronchiectasis confirmed by chest CT scan entered the study. Data from 106 patients were available for full evaluation. Clinical questionnaire, pulmonary function tests, sputum microbiology, laboratory data, and immune function testing were done. Results were analyzed by ethnicity and etiology. RESULTS: Patients were 61.6% European American (EA), 26.8% African American (AA), 8.9% Hispanic American (HA), and 2.7% Asian American. A cause of bronchiectasis was determined in 93.3% of patients. In 63.2% of patients, bronchiectasis was caused by immune dysregulation, including deficiency (n = 18 [17%]), autoimmune disease (n = 33 [31.1%]), hematologic malignancy (n = 15 [14.2%]), and allergic bronchopulmonary aspergillosis (n = 1 [0.9%]). Rheumatoid arthritis was the cause of bronchiectasis in 28.6% of AA patients vs 6.2% of EA patients (P < .05). Hematologic malignancy was the etiology in 20.0% of the EA patients vs none of the AA patients (P = .02). A significantly higher percentage of HA patients had Pseudomonas aeruginosa in their sputum compared with AA and EA patients (P = .01). CONCLUSIONS: The etiology of bronchiectasis can be determined in the majority of patients in a heterogeneous US population and is most often due to immune dysregulation. Rheumatoid arthritis is more likely in AA patients than EA patients. HA patients are more likely to have P aeruginosa in their sputum.