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Inhaled antibiotics are recommended conditionally by international bronchiectasis guidelines for the treatment of patients with bronchiectasis, but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have supplemented the existing body of evidence further in this area. To what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis? Systematic review and meta-analysis of randomized controlled trials of inhaled antibiotics in adult patients with bronchiectasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for eligible studies. Studies were included if they enrolled adults with bronchiectasis diagnosed by CT imaging and had a treatment duration of at least 4 weeks. The primary end point was exacerbation frequency, with additional key efficacy end points including severe exacerbations, bacterial load, symptoms, quality of life, and FEV 1. Data were pooled through random-effects meta-analysis. Twenty studies involving 3,468 patients were included. Inhaled antibiotics were associated with reduced number of patients with exacerbations (risk ratio, 0.85; 95% CI, 0.75-0.96), a slight reduction in exacerbation frequency (rate ratio [RR], 0.78; 95% CI, 0.68-0.91), a probable reduction in the frequency of severe exacerbations (RR, 0.48; 95% CI, 0.31-0.74), and a likely slight increase in time to first exacerbation (hazard ratio, 0.80; 95% CI, 0.68-0.94). Inhaled antibiotics likely lead to a slight increase in the Quality of Life Questionnaire-Bronchiectasis respiratory symptom score (mean difference, 2.51; 95% CI, 0.44-4.31) and may reduce scores on the St. George Respiratory Questionnaire (mean difference, –3.13; 95% CI, –5.93 to –0.32). Bacterial load consistently was reduced, but FEV 1 was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (OR, 0.99; 95% CI, 0.75-1.30). Antibiotic-resistant organisms likely were increased by treatment. In this systematic review and meta-analysis, inhaled antibiotics resulted in a slight reduction in exacerbations, a probable reduction in severe exacerbations, and a likely slight improvement in symptoms and quality of life in adults with bronchiectasis. International Prospective Register of Systematic Reviews; No.: CRD42023384694; URL: https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

Despite the coexistence of bronchiectasis and rheumatoid arthritis (RA) and the poor prognosis associated with the combination of conditions, to our knowledge, no longitudinal studies that comprehensively evaluated whether patients with RA have a higher risk of bronchiectasis compared with those without RA have been published. Whether seropositivity is associated with an increased risk of bronchiectasis in RA is the subject of ongoing controversy. Does RA influence the development of bronchiectasis? Is seropositivity associated with an increased risk of bronchiectasis in RA? The incidence of bronchiectasis was compared between individuals with RA (n = 50,651; seropositive rheumatoid arthritis [SPRA]: n = 35,879 and seronegative rheumatoid arthritis [SNRA]: n = 14,772) and 1:5 age- and sex-matched control patients (n = 253,255) enrolled between 2010 and 2017 in the Korean National Health Insurance Service database. The participants were followed from 1 year after RA diagnosis or the corresponding index date to the date of bronchiectasis incidence, censored date, or December 2019. The cumulative incidence of bronchiectasis at 9 years of follow-up was approximately 7% in participants with RA. During a median follow-up of 4.3 years (interquartile range, 2.6-6.3 years), participants with RA showed a 2.12-fold higher risk of developing bronchiectasis than matched control participants, even after adjusting for potential confounders related to bronchiectasis development (95% CI, 2.00-2.25). In an analysis of RA serologic status using a fully adjusted model, participants with SPRA and those with SNRA showed 2.34-fold (95% CI, 2.20-2.49) and 1.56-fold (95% CI, 1.40-1.73) increased risks, respectively, compared with matched control participants. Individuals with RA had approximately twice the risk of developing bronchiectasis than matched control individuals, even after adjusting for potential confounders. The increased risk was more evident in individuals with SPRA than in those with SNRA, implying that rheumatic inflammation plays a major role in the development of RA-bronchiectasis overlap. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation? In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens. The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD. [Display omitted] [ABSTRACT FROM AUTHOR]

Bronchiectasis, a previously neglected condition, now has renewed research interest. There are a few systematic reviews that have reported on the economic and societal burden of bronchiectasis in adults, but none have reported on children. We undertook this systematic review to estimate the economic burden of bronchiectasis in children and adults. What is the health care resource utilization and economic burden of bronchiectasis in adults and children? We performed a systematic review identifying publications from Embase, PubMed, Web of Science, Cochrane (trials, reviews, and editorials), and EconLit about the economic burden and health care utilization in adults and children with bronchiectasis between January 1, 2001, and October 10, 2022. We used a narrative synthesis approach and estimated aggregate costs for several countries. We identified 53 publications reporting on the economic burden and/or health care utilization of people with bronchiectasis. Total annual health care costs per adult patient ranged from 2021 $3,579 to $82,545 USD and were predominantly driven by hospitalization costs. Annual indirect costs including lost income because of illness (reported in only five studies) ranged from $1,311 to $2,898 USD. Total health care costs in children with bronchiectasis were $23,687 USD annually in the one study that estimated them. Additionally, one publication found that children with bronchiectasis missed 12 school days per year. We estimated aggregate annual health care costs for nine countries, ranging from $101.6 million per year in Singapore to $14.68 billion per year in the United States. We also estimated the aggregate cost of bronchiectasis in Australian children to be $17.77 million per year. This review highlights the substantial economic burden of bronchiectasis for patients and health systems. To our knowledge, it is the first systematic review to include the costs for children with bronchiectasis and their families. Future research to examine the economic impact of bronchiectasis in children and economically disadvantaged communities, and to further understand the indirect burden of bronchiectasis on individuals and the community, is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations. Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified? Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis. Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Māori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days. Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics. Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au [Display omitted] [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression. What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis? Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis. Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26). The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap. Is the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis? Electronic health care records (from 2004-2019) were used to obtain a cohort of patients with COPD and a nested case-control group (age and sex matched 1:4). Analyses were conducted to determine the risk of hospitalization for pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control group containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BECs) was used to determine any association with BEC. Three hundred sixteen thousand six hundred sixty-three patients were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (adjusted hazard ratio, 1.24; 95% CI, 1.15-1.33). In the first nested case-control group of 84,316 patients with COPD, ICS was found to increase the odds of pneumonia (adjusted OR [AOR], 1.26; 95% CI, 1.19-1.32) only if used in the previous 180 days. However, bronchiectasis was a significant modifier such that ICS use did not augment further the already elevated bronchiectasis-associated pneumonia risk (COPD-bronchiectasis: AOR, 1.01; 95% CI, 0.8-1.28; no bronchiectasis: AOR, 1.27; 95% CI, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control group confirmed these findings. Finally, we found that BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was associated significantly with pneumonia (BEC ≤ 3 × 109/L: AOR, 1.56; 95% CI, 1.05-2.31; BEC > 3 × 109/L: AOR, 0.89; 95% CI, 0.53-1.24). ICS use does not augment further the already increased risk of hospitalization for pneumonia associated with concomitant bronchiectasis in patients with COPD. [ABSTRACT FROM AUTHOR]

Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/μL), (2) low number of eosinophils (51-100/μL), (3) normal number of eosinophils (101-300/μL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/μL). Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/μL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/μL, 488 patients (52.6%) with 101-300 eosinophils/μL, and 153 patients (16.5%) with > 300 eosinophils/μL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/μL. A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.Research Question: What is the characteristic of MCD of the nasal epithelium and the association with disease severity and inflammatory endotypes in adults with bronchiectasis?Study Designs and Methods: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy controls who underwent brushing of nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n=13), elective surgery for bronchial epithelium biopsy (n=18), and blood sampling for next-generation sequencing (n=37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural [dynein axonemal heavy chain 5 (DNAH5), dynein intermediate chain 1 (DNAI1), radial spoke head protein 9 (RSPH9)] and ciliogenesis marker expression (Ezrin).Results: MCD was present in 89.8% of patients with bronchiectasis, 67.6% had secondary MCD and 16.2% had primary plus secondary MCD. Compared with healthy controls, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1 and RSPH9 (but not ezrin), which were more prominent in moderate-to-severe bronchiectasis. MCD pattern scores were largely consistent between upper and lower airways, and between large-to-medium and small airways in bronchiectasis. Co-existing nasal diseases and asthma did not significantly confound nasal ciliary ultrastructural marker expression. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly ultrastructural abnormality, was notable in patients with mild bronchiectasis who had blood or sputum eosinophilia.Interpretation: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis. [ABSTRACT FROM AUTHOR]

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a common comorbidity of nontuberculous mycobacteria (NTM) pulmonary disease (PD). Although GERD is associated with more symptoms and severe disease in patients with NTM PD, whether GERD is associated with an increased risk of NTM PD developing is unknown. Does GERD influence the development of NTM PD? Are there any factors associated with an increased risk of NTM PD among patients with GERD? What is the impact of NTM PD on the health-care use of patients with GERD? Data from the Korean National Health Insurance Service National Sample Cohort between 2002 and 2015 were used. The incidence and risk of NTM PD were compared between patients with GERD (GERD cohort; n = 17,424) and patients matched for age, sex, type of insurance, and Charlson Comorbidity Index (matched cohort; n = 69,696). Using the GERD cohort, the factors associated with incident NTM PD also were evaluated. During a median follow-up duration of 5.1 years, the age- and sex-adjusted incidence of NTM PD was significantly higher in the GERD cohort (34.8 per 100,000 person-years [PY]) than in the matched cohort (10.5 per 100,000 PY; P <.001), with a subdistribution hazard ratio (HR) of 3.36 (95% CI, 2.10-5.37). Regarding risk factors associated with NTM PD, age of 60 years or older (adjusted HR, 3.57; 95% CI, 1.58-8.07) and bronchiectasis (adjusted HR, 18.69; 95% CI, 6.68-52.28) were associated with an increased risk of incident NTM PD in the GERD cohort. Compared with patients with GERD who did not demonstrate NTM PD, those with NTM PD showed higher all-cause (13,321 PY vs 5,932 PY; P =.049) and respiratory disease-related (5,403 vs 801; P =. 011) ED visits or hospitalizations. GERD is associated with an increased incidence of NTM PD. Older age and bronchiectasis are risk factors for NTM PD in patients with GERD. NTM PD in patients with GERD is associated with increased health-care use. [Display omitted] [ABSTRACT FROM AUTHOR]

Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P <.05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P <.001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P =.012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P =.044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P =.012). Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice. Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. [ABSTRACT FROM AUTHOR]

Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log 10 colony-forming units/g; 95% CI, 1.12-2.35; P <.001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P <.001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. ClinicalTrials.gov; No. NCT03715322; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Case Presentation: A 13-year-old male patient with intermittent asthma and joint hypermobility presented to the ED in acute hypoxemic respiratory distress. He reported experiencing cough, increased work of breathing, and worsening chest pain for 3 days before presentation. He also reported fatigue and decreased appetite for 2 weeks. He had no known fever, myalgias, or recent weight loss. His medical history included two hospitalizations during early childhood for viral respiratory illnesses, one of which required intubation at 8 months of age. He had a gastrostomy tube placed shortly after his hospitalization because of failure to thrive secondary to aspiration based on a swallow study. His weight gain and growth improved with adequate nutrition, and his gastrostomy tube was removed at 2 years of age. His newborn screen, which included immunoreactive trypsinogen, was normal. He was noted to have hypermobile joints on physical examination at a clinic visit in childhood, but his examination results were not concerning for a hypermobility syndrome, and further diagnosis was not pursued. His parents endorsed that he has been a "healthy child" overall other than the occasional cough, which was attributed to asthma. His lifestyle was described as sedentary; he did not play any sports or have any unusual hobbies. He did not take any daily medications and no environmental exposures were reported. There was no family history of pulmonary, autoimmune, or connective tissue disease. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacterial (NTM) infections are difficult to diagnose and treat. Biomarkers to identify patients with active infection or at risk of disease progression would have clinical utility. Sputum is the most frequently used matrix for the diagnosis of NTM lung disease.Research Question: Can sputum proteomics be used to identify NTM-associated inflammatory profiles in sputum?Study Design and Methods: Patients with NTM lung disease and a matched cohort of patients with COPD, bronchiectasis (BE), and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the United Kingdom. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, and CF), the presence of NTM lung disease defined according to American Thoracic Society/Infectious Diseases Society of America criteria, and severity of NTM. A subset of patients receiving guideline-concordant NTM treatment were studied to identify protein changes associated with treatment response.Results: This study analyzed 95 sputum samples from 55 subjects (BE, n = 21; COPD, n = 19; CF, n = 15). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE, and CF found that 12 proteins were upregulated in CF compared with COPD, including MPO, AZU1, CTSG, CAT, and RNASE3, with 21 proteins downregulated, including SCGB1A1, IGFBP2, SFTPB, GC, and CFD. Across CF, BE, and COPD, NTM infection (n = 15) was not associated with statistically significant differences in sputum protein profiles compared with those without NTM. Two proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in the sputum protein profile. Patients with NTM and a decrease in immune response proteins had a subjective symptomatic improvement.Interpretation: Sputum proteomics identified candidate biomarkers of NTM severity and treatment response. However, underlying lung disease and typical bacterial pathogens such as P aeruginosa are also key determinants of the sputum proteomic profile. [ABSTRACT FROM AUTHOR]

Background: Population-based and retrospective studies have shown that risk for cardiovascular events such as arrythmias, ischemic episodes, or heart failure, increase during and after bronchiectasis exacerbations.Research Question: What are the risk factors for cardiovascular events (CVE) during and after bronchiectasis exacerbations and their impact on mortality?Study Design and Methods: This was a post hoc retrospective analysis of a prospective observational study of 250 patients with bronchiectasis at two tertiary care hospitals. Only the first exacerbation was considered for each patient, collecting demographic, comorbidity, and severity data. The main outcomes were the appearance of CVE and mortality. Risk factors for CVE were analyzed using a semi-competing risks model.Results: During a median follow-up of 35 months, 74 (29.6%) patients had a CVE and 93 (37.2%) died. Semi-competing risk analysis indicated that age, arterial hypertension, COPD, and potentially severe exacerbations significantly increased the risk for developing CVE. Compared with patients without CVE, those with CVE had higher mortality.Interpretation: Demographic factors and comorbidities are risk factors for the development of CVE after an acute exacerbation of bronchiectasis. The appearance of CVE worsens long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown.Research Question: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap?Study Design: Prospective, observational, cross-sectional study.Methods: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes.Results: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity.Conclusions: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an uncommon mycobacterial infection characterized by worsening lung function and increased health care resource utilization; however, the overall risk for hospitalization among patients with NTM-PD remains unclear.Research Question: What is the hospitalization risk among older adults with NTM-PD?Study Design and Methods: A retrospective, nested, case-control study was conducted by using the Medicare claims database. Cases were defined as patients with ≥ 2 NTM-PD claims ≥ 30 days apart between January 1, 2007, and December 31, 2015. The study included individuals aged ≥ 65 years with ≥ 12 months of continuous enrollment in both Parts A and B before the first NTM-PD diagnosis. Cases were matched 1:2 to Medicare beneficiaries without NTM-PD (control subjects) according to age and sex. Hospitalizations following the first NTM-PD claim were compared between case and control subjects by using univariate and multivariate analyses.Results: A total of 35,444 case subjects and 65,467 matched control subjects (mean age, 76.6 years; 70% female; ≥ 87% White) were identified. Baseline comorbidities, particularly pulmonary comorbidities, were more common in case subjects than in control subjects (81.1% vs 17.7% for COPD; 44.6% vs 0.6% for bronchiectasis). All-cause hospitalization was observed in 65.7% of case subjects and 44.9% of control subjects. Unadjusted annual hospitalization rates were significantly (P < .05) greater among case subjects than control subjects. Case subjects also had a significantly shorter time to hospitalization than control subjects. The increased burden due to hospitalization was reflected in multivariate analysis adjusting for baseline comorbidities. All-cause hospitalization in patients with NTM-PD relative to control subjects was 1.2 times more likely (relative risk, 1.23; 95% CI, 1.21-1.25; P < .0001) with a 46% greater hazard (hazard ratio, 1.46; 95% CI, 1.43-1.50; P < .0001).Interpretation: Patients with NTM-PD were significantly more likely to be hospitalized, had greater annualized hospitalization rates, and had shorter time to hospitalization than age- and sex-matched control subjects without NTM-PD. These findings highlight the significantly increased burden of hospitalizations among patients with NTM-PD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George's Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing., Research Question: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD?, Study Design and Methods: We investigated the proportion of PCD among the participants of the Prospective German Non-CF-Bronchiectasis Registry (PROGNOSIS) study; applied multiple imputation to account for missing data in 64 (FEV 1 ), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis., Results: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P < .001), age < 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P < .001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P = .016), duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P < .001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P = .007)., Interpretation: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02574143; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: I. P. reports grants from COFONI-2FF4 and COFONI-6LZF23 by the Ministry of Science and Culture of Lower Saxony paid to her institution and personal lecture fees from AstraZeneca and Boehringer Ingelheim. S. S. reports fees for clinical trial participation from Celtaxsys, Corbus, Galapagos, Insmed, Proteostasis, and Vertex Pharmaceuticals paid to his institution; and personal fees for consulting and lectures from Boehringer Ingelheim, Insmed, and Vertex Pharmaceuticals. S. P. A. reports personal consulting fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, and GlaxoSmithKline. A. G. reports personal fees for consulting, advisory board participation, and lectures from Boehringer Ingelheim and GlaxoSmithKline. A. S. reports personal fees for consulting and lectures from Ethris, Insmed, Spirovant, and Translate Bio; and is involved in the European Respiratory Society (ERS) Clinical Research Collaborations AMR-Lung, BEAT-PCD, and EMBARC. S. W. reports fees for clinical trial participation from Insmed paid to her institution and personal honoraria from Vertex Pharmaceuticals. P. M. reports fees for clinical trial participation from Boehringer Ingelheim and Insmed paid to his institution; reports personal fees for lectures from AstraZeneca, MAÄF eV, ResMed, and streamedup! GmbH; reports travel support from the German Society for Internal Medicine (DGIM), CSL Behring, and Insmed; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS. J. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), the Federal Ministry of Education and Research (BMBF), the Federal Ministry of Health (BMG), Novartis, and Insmed paid to her institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from AstraZeneca, Brahms GmbH, ERS, Grifols, Insmed, MedUpdate, MSD, Pfizer, Shionogi, and streamedup! GmbH; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS and chair of the Respiratory Infections and Tuberculosis Assembly of the German Respiratory Society (DGP). F. C. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), IMI (EU/EFPIA), and the Innovative Medicines Initiative (IMI) and EFPIA companies under the European Commission funded project, iABC [Grant 115721], Novartis, and Insmed Germany paid to his institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from Parion, Grifols, Zambon, Insmed, Helmholtz-Zentrum für Infektionsforschung, i!DE Werbeagentur GmbH, Interkongress GmbH, streamedup! GmbH, AstraZeneca, Insmed, Shionogi, and Grifols; reports travel support from the German Kartagener Syndrome and Primary Ciliary Dyskinesia patient advocacy group, which he serves as the unpaid co-speaker of its medical advisory board; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS, a member of the steering committee of the European Bronchiectasis Registry EMBARC, and a member of the Protocol Review Committee of the PCD-Clinical Trials Network. None declared (R. E., U. S., B. O. S.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous disease with a diverse clinical and genetic spectrum among populations worldwide. Few cases of pediatric PCD have been reported from China.Research Question: What are the clinical and genotypic characteristics of children with PCD in China?Study Design and Methods: Clinical characteristics, laboratory findings, and genetic results obtained for 75 patients with PCD were reviewed retrospectively at a single center in China. Genetic sequencing was conducted using whole-exome screening.Results: Patient median age at diagnosis was 7.0 years (range, 2 months-14 years). Of 75 patients, 88% (66/75) had chronic wet cough, 77% (58/75) had recurrent sinusitis, 76% (57/75) had bronchiectasis, 40% (30/75) had neonatal respiratory distress, and 28% (21/75) had coexistent asthma. Notably, postinfectious bronchiolitis obliterans (PIBO) as first presentation was found in 8% of children (6/75). Genes with the highest incidence of mutations were DNAH11 (15/51), followed by DNAH5 (9/51), CCDC39 (5/51), DNAH1 (4/51), and CCNO (3/51). Four genes (DNAI1, HEATR2, RSPH9, and DNAAF3) each were respectively found in two patients, and seven genes (CCDC40, LRRC6, SPAG1, RSPH4A, ARMC4, CCDC114, and DNAH14, a novel gene) each were mutated once. No differences in classical clinical features were observed among patients with commonly observed PCD-associated genotypes. However, three of six PIBO patients carried DNAH1 mutations.Interpretation: Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum. [ABSTRACT FROM AUTHOR]

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Until now, only three cases of lung transplantation for severe respiratory impairment have been reported. We describe a case of NPDB that was diagnosed after lung transplantation for cystic bronchiectasis. In 2016, a 31-year-old woman who was experiencing hypoxemic respiratory failure and recurrent pulmonary infections due to cystic bronchiectasis received a double-lung-transplantation. Histopathologic study on removed lungs revealed clusters of CD68 foamy lipid-laden macrophages with concentric and palisade arrangement, compatible with the diagnosis of NPDB, which was confirmed after SMPD1 genetic sequencing. Twenty-three months after transplantation, allograft function is stable (FEV1 was 100% of best-FEV1). The singularity of this case lies in the presence of bronchiectasis, which is an unprecedently described phenotype of NPDB. This finding was accompanied by the detection of a novel SMPD1 mutation (p.Ala46=) of uncertain meaning. [ABSTRACT FROM AUTHOR]

Background: Clinical heterogeneity in bronchiectasis remains a challenge for improving the appropriate targeting of therapies and patient management. Antimicrobial peptides (AMPs) have been linked to disease severity and phenotype.Research Question: Can we identify clusters of patients based on the levels of AMPs, airway inflammation, tissue remodeling, and tissue damage to establish their relationship with disease severity and clinical outcomes?Study Design and Methods: A prospective cohort of 128 stable patients with bronchiectasis were recruited across three centers in three different countries (Spain, Scotland, and Italy). A two-step cluster strategy was used to stratify patients according to levels of lactoferrin, lysozyme, LL-37, and secretory leukocyte protease inhibitor in sputum. Measurements of inflammation (IL-8, tumor growth factor β, and IL-6), tissue remodeling and damage (glycosaminoglycan, matrix metallopeptidase 9, neutrophil elastase, and total and bacterial DNA), and neutrophil chemotaxis were assessed.Results: Three clusters of patients were defined according to distinct airway profiles of AMPs. They represented groups of patients with gradually distinct airway infection and disease severity. Each cluster was associated with an airway profile of inflammation, tissue remodeling, and tissue damage. The relationships between soluble mediators also were distinct between clusters. This analysis allowed the identification of the cluster with the most deregulated local innate immune response. During follow-up, each cluster showed different risk of three or more exacerbations occurring (P = .03) and different times to first exacerbations (P = .03).Interpretation: Bronchiectasis patients can be stratified in different clusters according to profiles of airway AMPs, inflammation, tissue remodeling, and tissue damage. The combination of these immunologic variables shows a relationship with disease severity and future risk of exacerbations. [ABSTRACT FROM AUTHOR]

Some severe asthmatic patients experience frequent bacterial respiratory tract infections, which contribute significantly to their disease burden, and often are attributed to their use of systemic corticosteroids and comorbid bronchiectasis. We report a case of a 58-year-old woman who had prednisone-dependent asthma and exacerbations with intense mixed eosinophilic and neutrophilic bronchitis. Autosomal dominant hyper-IgE syndrome, which is a primary immunodeficiency characterized by elevated IgE, eosinophilia, and recurrent infections, caused by a novel pathogenic mutation in STAT3 was identified as the cause of her airway disease. We believe that this is the first report of the demonstration of an IL-5 driven eosinophilia that is associated with a STAT3 mutation that was treated successfully with an anti-IL5 biological. [ABSTRACT FROM AUTHOR]

Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable. [ABSTRACT FROM AUTHOR]

B, Frequency and C, annual prevalence of coexisting non-TB mycobacterium infection in patients with non-cystic fibrosis bronchiectasis stratified by sex, 2012-2016. D, Number of outpatient clinic visits and E, medical costs between bronchiectasis patients with non-TB mycobacterium infection and those patients without non-TB mycobacterium infection. To the Editor: Epidemiologic research has shown that the prevalence and incidence of non-cystic fibrosis (CF) bronchiectasis are gradually increasing.[1] SP , sp [2] Recent epidemiologic data also revealed that the prevalence and incidence of non-tuberculous mycobacterium (NTM) infection increased rapidly from 2003 to 2016.[3] However, data regarding NTM infection in patients with non-CF bronchiectasis are relatively insufficient. [Extracted from the article]

To the Editor: Fungal infection in association with lung disease has emerged as a significant clinical problem.[1] Owing to a ubiquitous environmental abundance, fungal spores, inhaled daily, can reach even the smallest airways.[2] SP , sp [3] Although healthy individuals have effective immune mechanisms to clear this, individuals with anatomically abnormal airways and chronic respiratory disease (CRD) such as bronchiectasis are at higher risk of colonization and complications.[[2]] Use of high-throughput sequencing has allowed insight into the pulmonary microbiome. We have previously identified Candida, Penicillium, and Saccharomyces in healthy control subjects and in patients with bronchiectasis.[3] We showed that the bronchiectasis mycobiome is distinct and characterized by pathogenic fungal genera, including Aspergillus, Cryptococcus, and Clavispora. The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis [published online ahead of print June 13, 2020]. [Extracted from the article]

Background: Chronic wet cough in children is the hallmark symptom of protracted bacterial bronchitis (PBB) and if left untreated can lead to bronchiectasis, which is prevalent in Indigenous populations. Underrecognition of chronic wet cough by parents and clinicians and underdiagnosis of PBB by clinicians are known.Research Question: We aimed to improve recognition and management of chronic wet cough in Aboriginal children using knowledge translation (KT), a methodologic approach that can be adapted for use in Indigenous contexts to facilitate effective and sustained translation of research into practice.Study Design and Methods: A mixed-methods KT study undertaken at a remote-based Aboriginal primary medical service (February 2017 to December 2019). Our KT strategy included the following: (1) culturally secure (ie, ensuring Aboriginal people are treated regarding their unique cultural needs and differences) knowledge dissemination to facilitate family health seeking for chronic wet cough in children, and (2) an implementation strategy to facilitate correct diagnosis and management of chronic wet cough and PBB by physicians.Results: Post-KT, health seeking for chronic wet cough increased by 184% (pre = eight of 630 children [1.3%], post = 23 of 636 children [3.6%]; P = .007; 95% CI, 0.7%-4.0%). Physician proficiency in management of chronic wet cough improved significantly as reflected by improved chronic cough-related quality of life (P < .001; 95% CI, 0.8-3.0) and improved physician assessment of cough quality (P < .001; 95% CI, 10.4%-23.0%), duration (P < .001; 95% CI, 11.1%-24.1%), and appropriate antibiotic prescription (P = .010; 95% CI, 6.6%-55.7%).Interpretation: Health seeking for children with chronic wet cough can be facilitated through provision of culturally secure health information. Physician proficiency in the management of PBB can be improved with KT strategies which include training in culturally informed management, leading to better health outcomes. Comprehensive strategies that include both families and health systems are required to ensure that chronic wet cough in children is detected and optimally managed. [ABSTRACT FROM AUTHOR]

Background: Pulmonary exacerbations in cystic fibrosis are characterized by airway inflammation and may cause irreversible lung damage. Early identification of such exacerbations may facilitate early initiation of treatment, thereby potentially reducing long-term morbidity.Research Question: Is it possible to predict pulmonary exacerbations in children with cystic fibrosis, using inflammatory markers obtained from BAL fluid?Study Design and Methods: A longitudinal analysis was conducted of children aged 0 to 7 years included in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) study between 2005 and 2015. The association between inflammatory markers from annual BAL fluid and time to pulmonary exacerbation requiring hospital admission in the 6-month period post-BAL was analyzed using Kaplan-Meier curves and Weibull regression, adjusting for annually repeated measurements. Admissions for Pseudomonas eradication were excluded in the main analysis, because of the standard policy in participating centers to treat Pseudomonas in-hospital.Results: Nine hundred seventy-six BAL samples from 308 children were analyzed. After exclusion of admissions for Pseudomonas eradication (n = 43), there were 145 pulmonary exacerbations recorded within 6 months of BAL; median time to exacerbation was 31 days (interquartile range, 9-100). In univariate analyses, high IL-8 (hazard ratio [HR], 2.25 for 75th vs 25th percentile; 95% CI, 1.87-2.72), neutrophil elastase (HR, 3.00; 95% CI, 2.03-4.42), and high neutrophil percentage (HR, 1.80 for 75th vs 25th percentile; 95% CI, 1.56-2.04) were all significantly associated with risk for a pulmonary exacerbation (P < .001). The inflammatory markers remained significant predictors after adjustment for clinical predictive variables.Interpretation: Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis. The development of noninvasive measures of lung inflammation may facilitate routine surveillance of cystic fibrosis. [ABSTRACT FROM AUTHOR]

Background: In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies.Research Question: What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up?Study Design and Methods: Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow up. The association between ACT use and clinical outcomes was assessed with the use of unadjusted and adjusted multinomial logistic regression models.Results: Of the overall study population (n = 905), 59% used ACTs at baseline. A greater proportion of patients who used ACTs at baseline and follow up continuously had Pseudomonas aeruginosa (47% vs 36%; P = .021) and experienced an exacerbation (81% vs 59%; P < .0001) or hospitalization for pulmonary illness (32% vs 22%; P = .001) in the prior two years, compared with those patients who did not use ACTs. Fifty-eight percent of patients who used ACTs at baseline did not use ACTs at 1-year follow up. There was no significant change in pulmonary function for those who used ACTs at follow up, compared with baseline. Patients who used ACTs at baseline and follow up had greater odds for experiencing exacerbations at follow up compared with those patients who did not use ACTs.Interpretation: In patients with bronchiectasis and a productive cough, ACTs are used more often if the patients have experienced a prior exacerbation, hospitalization for pulmonary illness, or had P aeruginosa. There is a significant reduction in the use of ACTs at 1-year follow up. The odds of the development of a bronchiectasis exacerbation are higher in those patients who use ACTs continuously, which suggests more frequent use in an ill bronchiectasis population. [ABSTRACT FROM AUTHOR]

Background: Inequitable access to quality health care contributes to the known poorer outcomes of people living in regional/remote areas (compared with urban-based), especially for First Nations people. Integration of specialist outreach services within primary care is one strategy that can reduce the inequity when modeled to the needs and available resources of target communities.Research Question: To evaluate whether respiratory outreach clinics in regional and remote Queensland are as effective as tertiary respiratory services at improving the lung function of children.Study Design and Methods: From existing databases, we obtained spirometry data of children (aged 3-18 years) seen at Indigenous-focused outreach clinics in regional and remote Queensland and Brisbane-based pediatric tertiary hospitals over the same contemporary period (October 2010 to July 2019). We compared the change in spirometry z scores (Δz) at follow-up for both groups of children.Results: Lung function significantly improved in both groups: Tertiary hospital (n = 2,249; ΔzFEV1 = 0.22, 95% CI, 0.17 to 0.27; ΔzFVC = 0.23, 95% CI, 0.18 to 0.28); outreach (n = 252; ΔzFEV1 = 0.35, 95% CI, 0.22 to 0.48; ΔzFVC = 0.36, 95% CI, 0.23 to 0.50). No significant intergroup differences were found in ΔzFEV1 (0.13; 95%CI, -0.02 to 0.28; P = .10) or ΔzFVC (0.14; 95% CI, -0.02 to 0.29; P = .08) improvement from baseline. In both groups, the proportion of children with zFEV1 > 0 at follow-up (hospital = 31.7%; outreach = 46.8%) significantly increased (hospital P = .001; outreach P = .009) from baseline (hospital = 27.2%; outreach = 35.3%). Numbers of children with zFEV1 > 0 significantly increased for asthma and bronchiectasis outreach subgroups, and for children with asthma in the hospital-based group.Interpretation: Comparable significant lung function improvement of children was seen in Indigenous-focused outreach remote/regional clinics and paediatric tertiary hospitals. This suggests that effective clinical care is achievable within the outreach setting. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To the Editor: Non-TB mycobacteria (NTM) are becoming increasingly recognized as clinically significant pathogens in lung transplant recipients (LTRs).[[1]] Owing to advanced pulmonary disease among lung transplantation (LTX) candidates, patients could have a history of remote or current NTM-pulmonary disease (PD), or it could be detected incidentally after being listed for LTX. Posttransplantation NTM-PD and Overall Outcome In follow up until December 2017, posttransplantation NTM-PD developed in 11.1% of LTRs (2/18 patients) with peritransplantation NTM-PD (11 and 12 months after NTM management protocol, respectively) vs 6.6% of LTRs (14/212 patients) without peritransplantation NTM-PD (median, 10 months after transplantation; P =.362). To sum up, patients with NTM-PD diagnosed at the time of LTX and treated according to the protocol were safely managed and did not experience significantly greater rates of post-transplant NTM-PD, CLAD and survival. [Extracted from the article]