A systematic literature review of the clinical and socioeconomic burden of bronchiectasis.

BACKGROUND: The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162). METHODS: Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017-December 2022). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included. Editorials, narrative reviews and systematic literature reviews were included to identify primary studies. PRISMA guidelines were followed. RESULTS: 1585 unique publications were identified, of which 587 full texts were screened and 149 were included. A further 189 citations were included from reference lists of editorials and reviews, resulting in 338 total publications. Commonly reported symptoms and complications included dyspnoea, cough, wheezing, sputum production, haemoptysis and exacerbations. Disease severity across several indices and increased mortality compared with the general population was reported. Bronchiectasis impacted quality of life across several patient-reported outcomes, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation was considerable and substantial medical costs related to hospitalisations, treatments and emergency department and outpatient visits were accrued. Indirect costs included sick pay and lost income. CONCLUSIONS: Bronchiectasis causes significant clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce both healthcare resource utilisation and overall costs are needed. Further systematic analyses of specific aetiologies and paediatric disease may provide more insight into unmet therapeutic needs.

Early and late outcomes of video thoracoscopic versus open approach for bronchiectasis lung resections.

OBJECTIVES: To evaluate the early and late results of surgical treatment of patients with bronchiectasis, comparing the Video-Assisted Thoracic Surgery (VATS) vs. the open thoracotomy (OT). METHODS: Observational retrospective study of patients who underwent surgery for bronchiectasis. Patients were divided into two groups according to surgical access OT/VATS. Variables collected included gender, age, preoperative symptoms, etiology, segments involved, FVC and FEV1, type of surgical resection, complications, mortality, and length of hospital stay. Late surgical results were classified as excellent, complete remission of symptoms; good, significative improvement; and poor, little/no improvement. RESULTS: 108 surgical resections (103 patients). OT group 54 patients (52.4%) vs. VATS 49 (47.6%). A high percentage of complications was observed, but no difference between the OT (29.6%) and VATS (24.5%) groups was found. Post-operative hospital stay was shorter in the VATS group (5.4 days) vs. the OT group (8.7 days (p=0.029). 75% of the patients had a late follow-up; the results were considered excellent in 71.4%, good in 26%, and poor in 2.6%. Regarding bronchiectasis distribution, an excellent percentage was obtained at 82.1% in patients with localized bronchiectasis and 47.5% with non-localized bronchiectasis, p=0.003. CONCLUSIONS: VATS leads to similar results regarding morbidity, compared to OT. However, VATS was related to shorter hospital stays, reflecting the early recovery. Late results were excellent in most patients, being better in patients with localized bronchiectasis. VATS should be considered a preferable approach for bronchiectasis lung resection whenever possible.

[The impact of diabetes on bronchiectasis].

Objective: To study the impact of diabetes on bronchiectasis. Methods: From January 1 2017 to December 31 2021, data of 1 310 inpatients with bronchiectasis were retrospectively collected from Shanghai Pulmonary Hospital, Tongji University. This cohort inclueded 78 patients with bronchiectasis and diabetes (bronchiectasis-diabetes group) and 1 232 patients of bronchiectasis without diabetes (simple bronchiectasis group). To mitigate confounding variables, 269 patients with bronchiectasis but without diabetes (bronchiectasis non-diabetes group) were matched with 78 patients of bronchiectasis with diabetes (bronchiectasis-diabetes group) using the propensity score method in a 1∶4 ratio. A comparative analysis of clinical characteristics, laboratory test results, pathogenic infections, and disease severity was performed between the two groups. Analysis of continuous variables was performed using either a t-test or non-parametric test, while categorical data was assessed using the chi-square test. Results: The mean age of individuals in the bronchiectasis-diabetes group (62.99±8.09 years) was significantly higher than that of subjects in the simple bronchiectasis group (57.05±13.07 years) (t=-6.012, P<0.001). After propensity score matching, the pre-albumin level in the bronchiectasis-diabetes group (188.44±71.65 g/L) was found to be lower than in the bronchiectasis non-diabetes group (208.17±62.50 g/L) (t=2.023, P=0.044). In addition, the hospitalization cost for the bronchiectasis-diabetes group [1.59 (1.34, 2.15) Ten thousand yuan] was higher than that in the bronchiectasis non-diabetes group [1.39 (1.23, 1.62) Ten thousand yuan] (U=-3.744, P<0.001).The severity of mMRC in the bronchiectasis-diabetes group was significantly higher than that in the bronchiectasis non-diabetes group (χ2=25.392, P<0.001), and the frequency of previous hospitalization due to aggravation and acute exacerbation within the previous year were higher than in bronchiectasis non-diabetes group (χ2=34.031, 40.841, respectively, P<0.001). In additional, the BSI score was significantly increased in patients with bronchiectasis-diabetes compared to those with bronchiectasis non-diabetes (8.07±4.07 vs. 10.44±3.82) (P<0.001). Furthermore, fasting blood glucose concentration, urine glucose level, and BSI score exhibited positive correlations, whereas pre-albumin concentration showed a negative correlation with the BSI score (all P<0.05). Conclusion: Compared to those without diabetes, patients of bronchiectasis with diabetes have poorer nutritional status, more severe symptoms, increased risk of acute exacerbation, higher BSI score severity, and greater financial burden.

Incidence of bronchiectasis in patients with acromegaly: a cohort study.

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis. Materials and methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis.

Nontuberculous mycobacterial pulmonary disease presenting as bronchiolitis pattern on CT without cavity or bronchiectasis.

BACKGROUND: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). METHODS: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. RESULTS: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2-3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time. CONCLUSION: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.

Bronchiectatic Actinomycosis with Osseous Metaplasia Masquerading as Lung Cancer.

After the publication of the original article, the authors noticed an error in the departmental affiliation of one of the contributors, Don MASCARENHAS. The corrected version of the department is provided below, and the original article has been updated accordingly. Archana BHAT < sup > 1 < /sup > , Manjunath J < sup > 1 < /sup > , Don MASCARENHAS < sup > 2 < /sup > < br / > Department of < sup > 1 < /sup > Pathology and < sup > 2 < /sup > Pulmonology, Father Muller Medical College, MANGALORE, INDIA.

Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.

New-onset obstructive airway disease following COVID-19: a multicenter retrospective cohort study.

BACKGROUND: The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. METHODS: This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22-1.33; p < 0.001). Stratified analyses by age, SARS-CoV-2 variant, vaccination status, and infection status consistently supported this association. Non-hospitalized individuals with COVID-19 demonstrated a higher risk of new-onset asthma (aHR, 1.27; 95% CI, 1.22-1.33; p < 0.001); however, no significant differences were observed in hospitalized and critically ill groups. The study also identified an increased risk of subsequent bronchiectasis following COVID-19 (aHR, 1.30; 95% CI, 1.13-1.50; p < 0.001). In contrast, there was no significant difference in the hazard of chronic obstructive pulmonary disease between the groups (aHR, 1.00; 95% CI, 0.95-1.06; p = 0.994). CONCLUSION: This study offers convincing evidence of the association between COVID-19 and the subsequent onset of asthma and bronchiectasis. It underscores the need for a multidisciplinary approach to post-COVID-19 care, with a particular focus on respiratory health.

Investigating pulmonary and non-infectious complications in common variable immunodeficiency disorders: a UK national multi-centre study.

Background: Common Variable Immunodeficiency Disorders (CVID) encompass a spectrum of immunodeficiency characterised by recurrent infections and diverse non-infectious complications (NICs). This study aimed to describe the clinical features and variation in NICs in CVID with and without interstitial lung disease (ILD) from a large UK national registry population. Methods: Retrospective, cross-sectional data from a UK multicentre database (previously known as UKPIN), categorising patients into those with CVID-ILD and those with NICs related to CVID but without pulmonary involvement (CVID-EP; EP= extra-pulmonary involvement only). Results: 129 patients were included. Chronic lung diseases, especially CVID-ILD, are prominent complications in complex CVID, occurring in 62% of the cohort. Bronchiectasis was common (64% of the cohort) and associated with greater pulmonary function impairment in patients with CVID-ILD compared to those without bronchiectasis. Lymphadenopathy and the absence of gastrointestinal diseases were significant predictors of ILD in complex CVID. Although the presence of liver disease did not differ significantly between the groups, nearly half of the CVID-ILD patients were found to have liver disease. Patients with CVID-ILD were more likely to receive immunosuppressive treatments such as rituximab and mycophenolate mofetil than the CVID-EP group, indicating greater need for treatment and risk of complications. Conclusion: This study highlights the significant burden of CVID-ILD within the CVID population with NICs only. The lungs emerged as the most frequently affected organ, with ILD and bronchiectasis both highly prevalent. These findings emphasise the necessity of a comprehensive and multidisciplinary approach in managing CVID patients, considering their susceptibility to various comorbidities and complications.

Bronchiectasis in Asia: a review of current status and challenges.

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China. Asian patients with bronchiectasis are less likely to show female predominance and experience exacerbations, are more likely to be younger, have milder disease, and have fewer options for guideline-recommended treatment than those living in other global regions. Furthermore, Asian bronchiectasis patients demonstrate different comorbidities, microbiological profiles and unique endophenotypes, including post-tuberculosis and dry bronchiectasis. Notably, each Asian region reveals further geographic variations and inter-patient differences. Future studies are warranted to better characterise Asian patients with bronchiectasis.

Síndrome de Williams-Campbell: reporte de caso / Williams-Campbell Syndrome: Case Report

El síndrome de Williams-Campbell (SWC) es una entidad clínica caracterizada por la deficiencia de cartílago en la pared bronquial de los bronquios subsegmentarios. Es una condición congénita que por lo general se diagnostica en la niñez, pero hay reportes de caso en la población adulta y se cree que esto se debe a un menor déficit de cartílago. Los síntomas principales de esta condición son la presencia de tos, disnea e infecciones respiratorias a repetición. Radiológicamente, se evidencia la presencia de bronquiectasias de pared delgada. El diagnóstico se basa en descartar otras causas más comunes de bronquiectasias, así como en la identificación de las características radiológicas y la presencia del componente congénito. Presentamos el caso de un joven con síntomas respiratorios desde la infancia, con necesidad de múltiples hospitalizaciones por procesos infecciosos de origen pulmonar a repetición, con lo cual se llega al diagnóstico de un síndrome de Williams-Campbell.

Williams-Campbell syndrome (WCS) is a clinical entity characterized by cartilage deficiency in the bronchial wall of the subsegmental bronchi. It is a congenital condition that is usually diagnosed in childhood, but there are case reports in the adult population, and it is believed that this is due to a minor cartilage deficiency. The main symptoms of this condition are the presence of cough, dyspnea and repeated respiratory infections. Radiologically, the presence of thin-walled bronchiectasis is evident. The diagnosis is based on ruling out other more common causes of bronchiectasis, as well as identifying the radiological characteristics and the presence of the congenital component. We present the case of a young man with respiratory symptoms since childhood requiring multiple hospitalizations due to repeated infectious processes of pulmonary origin, in which the diagnosis of Williams-Campbell syndrome was reached.

Real-world treatment patterns, health care resource utilization, and costs in a US Medicare population with bronchiectasis.

BACKGROUND: Bronchiectasis carries a significant economic burden with high health care expenditures associated with frequent hospitalizations, physician visits, and treatments, including oral and intravenous antibiotics for repeated lung infections, airway-clearance therapy, and oxygen administration. Bronchiectasis exacerbations can contribute to this burden. OBJECTIVE: To estimate US health care resource utilization (HCRU) and costs associated with bronchiectasis and with bronchiectasis exacerbations. METHODS: This retrospective study used the 100% Medicare Fee-for-Service database (January 2014 to December 2020) to compare HCRU and costs among patients with bronchiectasis with those of patients without bronchiectasis (controls). For patients with bronchiectasis, the index date was a randomly selected bronchiectasis claim after more than 1 year of disease history and, for controls, a claim closest to their matched bronchiectasis patient's index date. All patients had continuous enrollment for at least 12 months pre-index (baseline) and at least 12 months post-index. Primary outcomes were all-cause, respiratory-related, and bronchiectasis-related HCRU and health care costs, which were presented by the overall sample and by segmented patient cohorts based on the number of exacerbations during baseline (0, 1, or ≥2). RESULTS: 92,529 patients with bronchiectasis (mean [SD] age, 76.7 [8.8] years; 72.3% female) and 92,529 matched controls qualified for the study. Compared with controls, patients with bronchiectasis presented greater mean (SD) all-cause physician visits (15.4 [10.0] vs 13.2 [9.7]; P < 0.001) and respiratory-related physician visits (5.2 [4.3] vs 1.9 [3.1]), pulmonologist visits (1.9 [2.2] vs 0.3 [1.0]), hospitalizations (0.4 [0.9] vs 0.3 [0.8]), emergency department visits (0.33 [1.0] vs 0.26 [1.0]), and total health care costs ($10,224 [$23,263] vs $6,704 [$19,593]). Respiratory-related HCRU was also greater in patients with more baseline exacerbations, with total health care costs of $8,506, $10,365, and $14,790 for patients with 0, 1, and at least 2 exacerbations, respectively (P < 0.01). CONCLUSIONS: This real-world study demonstrates the high disease burden associated with bronchiectasis and with exacerbations, highlighting the need to improve management and reduce exacerbations.

Development and validation of a novel questionnaire to describe and assess sensations and triggers associated with refractory and unexplained chronic cough.

INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.

The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study.

BACKGROUND: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). METHODS: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. RESULTS: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1ß, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. CONCLUSION: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Construction of a panoramic mRNA map of adult noncystic fibrosis bronchiectasis and a preliminary study of the underlying molecular mechanisms.

BACKGROUND: The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation. METHODS: The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman's correlation analysis was used to analyse the correlation between DEGs and clinical indicators. RESULTS: Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P < 0.05). CONCLUSIONS: Transcriptomic methods were used to construct a panoramic map of bronchiectasis mRNA expression. The findings showed that neutrophil activation, chronic inflammation, immune regulation, impaired ribosomal function, oxidative phosphorylation, and energy metabolism disorders are important factors in the development of bronchiectasis. VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 may play important roles in the pathogenesis of bronchiectasis and are potential therapeutic targets.

Clinical perspectives in bronchiectasis management.

Non-cystic fibrosis bronchiectasis is a chronic inflammatory airway disease that results in permanent lung damage and can correlate with considerable clinical and economic burden. There are gaps in knowledge surrounding bronchiectasis, for which there are no published US-based treatment guidelines or FDA-approved therapies. Given the current challenges and gaps in care, the authors of this article convened for an AJMC® roundtable in March 2024. This publication summarizes the main findings of that roundtable and situates them in a scholarly context. Panelists agreed that patients with unexplained chronic cough or fatigue, purulent sputum production, hemoptysis, or repeated infection should undergo CT scanning to assess the presence of bronchiectasis, which has been estimated to affect approximately 364,000 to 558,000 individuals at least 18 years of age. They noted that disease symptoms and treatment burden can considerably diminish patient health-related quality of life (HRQOL) and that an exacerbation uniformly signifies deteriorating health and substantially impacts disease progression, hospitalization rates, and mortality. Absent an FDA-approved therapy, panelists' top management priorities were preventing or reducing exacerbations and maintaining or improving HRQOL. Panelists concluded that providers are ill-equipped to change the course of this heterogenous disease and that there is a real need for options to manage symptoms, for US-based guidelines, and for more research into epidemiology, etiology, and treatment.

Patient pathways for four major chronic respiratory diseases in England between 2008 and 2021.

BACKGROUND: Not all chronic diseases have clear pathways and time targets for diagnosis. We explored pathways and timings for four major chronic respiratory diseases in England. METHODS: Using deidentified electronic healthcare records from Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, we derived cohorts of patients diagnosed with asthma, chronic obstructive pulmonary disease (COPD), ILD or bronchiectasis at three time periods (2008/2009, 2018/2019 and 2020/2021). We followed people 2 years before and 2 years after diagnosis, calculating the proportion of people who presented with symptoms, underwent diagnostic tests, were treated and consulted healthcare (primary or secondary) and calculated time intervals between events. We repeated analyses by socioeconomic status and geographical region. RESULTS: We descriptively studied patient pathways for 429 619 individuals across all time frames and diseases. Most people (>87%) had first evidence of diagnosis in primary care. The proportion of people reporting symptoms prior to diagnosis was similar for asthma, COPD and ILD (41.0%-57.9%) and higher in bronchiectasis (67.9%-71.8%). The proportion undergoing diagnostic tests was high for COPD and bronchiectasis (77.6%-89.2%) and lower for asthma (14%-32.7%) and ILD (2.6%-3.3%). The proportion of people undergoing diagnostic tests decreased in 2020/2021 for all diseases, mostly COPD. Time (months) (median (IQR)) between symptoms and diagnosis, averaged over three time periods, was lowest in asthma (~7.5 (1.3-16.0)), followed by COPD (~8.6 (1.8-17.2)), ILD (~10.1 (3.6-18.0)) and bronchiectasis (~13.5 (5.9-19.8)). Time from symptoms to diagnosis increased by ~2 months in asthma and COPD over the three time periods. Although most patients were symptomatically treated prior to diagnosis, time between diagnosis and postdiagnostic treatment was around 4 months for ILD, 3 months for bronchiectasis and instantaneous for asthma and COPD. Socioeconomic status and regional trends showed little disparity. CONCLUSION: Current pathways demonstrate missed opportunities to diagnose and manage disease and to improve disease coding.

Pseudomonas aeruginosa mucinous phenotypes and algUmucABD operon mutant characteristics obtained from inpatients with bronchiectasis and their correlation with acute aggravation.

Objective: Although the mechanism is unclear, Pseudomonas aeruginosa (PA) infection directly affects the frequency of acute exacerbations in patients with bronchiectasis. The aims of this article are to analyze the genetic mutation characteristics of the algUmucABD operon in PA, isolated from hospitalized patients with bronchiectasis, and to explore independent risk factors for frequent acute exacerbations of bronchiectasis. Methods: Based on the number of acute exacerbations that occurred in the past year, these patients with bronchiectasis were divided into those with frequent acute exacerbations (Group A) and those with non-frequent acute exacerbations (Group B). We identified the distribution of mucoid phenotypes (MPs) and alginate morphotypes (AMs) in PA, and classified them into I-IV categories based on their different AMs; otherwise, the gene mutation types (GMTs) of the algUmucABD operon were tested. Subsequently, the relationship between GMT, MP, and AM and the independent risk factors for frequent acute exacerbations in patients with bronchiectasis were explored. Results: A total of 93 patients and 75 PA strains, from January 2019 to August 2023, were included in this study. The MP and AM distributions of PA were as follows: 64 strains (85.33%) of mucoid (the AMs were 38 strains of type I, 3 strains of type II, and 23 strains of type IV) and 11 strains of non-mucoid (the AM was type III only). Mucoid PA with algU, mucA, mucB, and mucD mutations accounted for 19.61%, 74.51%, 31.37%, and 50.98%, respectively. GMT was divided into the following: mucA mutations only, mucA combined with other gene mutations, other gene mutations without mucA mutations, and without gene mutations. In 91.7% of PA with type I of AM, only mucA mutations occurred, and in both separate MP and AM, the GMT differences were statistically significant. Lastly, the number of lung lobes with bronchiectasis and the number of PA with mucA mutations only were the independent risk factors for frequent acute exacerbations. Conclusion: The mucA mutation was primarily responsible for the mucoid of MP and type I of AM in PA, and it was also an independent risk factor for frequent exacerbations of bronchiectasis.

Current physiotherapy practice for adults with bronchiectasis: Data from the Australian bronchiectasis registry.

BACKGROUND: Although airway clearance techniques (ACTs) and physical exercise are recommended for adults with bronchiectasis, there is little data on current practice and limited guidance predicting clinical approach. OBJECTIVE: This study aimed to describe current ACT and exercise practice recorded by patients, and identify predictors of regular ACTs, ACT modalities and exercise. METHODS: Physiotherapy-specific interventions, quality of life (Quality-of-Life Bronchiectasis questionnaire, QOL-B), demographics and disease severity were extracted from the Australian Bronchiectasis Registry. Multivariate analyses were undertaken to identify predictors of undertaking ACTs or exercise. RESULTS: We included 461 patients; median age of 72 years (interquartile range 64-78 years). Regular ACT use was recorded by 266 (58 %) patients; the active cycle of breathing technique (n = 175, 74 %) was the most common technique. Regular exercise use was recorded by 213 (46 %) patients, with walking the most common form of exercise. A pulmonary rehabilitation referral was made for 90 (19.5 %) of patients. Regular ACT use was associated with a higher treatment burden on QOL-B (Odds ratio (OR) = 0.97, 95 % confidence interval (CI) 0.96 to 0.99). Regular exercise was more likely amongst patients with severe bronchiectasis compared to those with mild disease (OR = 9.46, 95 % CI 1.94 to 67.83) and in those with greater physical function on the QOL-B (OR = 1.02, 95 % CI 1.01 to 1.04). CONCLUSION: Approximately half the adults in the registry report regular ACT or exercise; QOL and disease severity predict this engagement. This knowledge may guide the tailoring of ACTs and exercise prescription to optimise physiotherapy management in adults with bronchiectasis.