Deciphering the microbial landscape of lower respiratory tract infections: insights from metagenomics and machine learning.

Background: Lower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types. Method: We collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria. Result: We observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time. Conclusion: Our study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

Bronchiectasis After Solid-Organ Transplant: A Retrospective Single Center Study.

OBJECTIVES: Bronchiectasis is characterized by abnormal, persistent, and irreversible enlargement of the bronchi. Many etiological factors have been described, but there are limited data on the development of bronchiectasis after organ transplantation. Our study is the first to study evaluate the frequency of bronchiectasis in heart and liver transplants as well as kidney transplants. Our aim is to analyze the frequency of bronchiectasis development after solid-organ transplant and the characteristics of the cases and to evaluate potential relationships. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent solid-organ transplant at the Baskent University Faculty of Medicine Hospital through the hospital electronic information system. Demographic, clinical, and laboratory data and thoracic computed tomography scans were evaluated. RESULTS: The study included 468 patients (151 females/317 males). Kidney transplant was performed in 61.5% (n = 207), heart transplant in 20.3% (n = 95), and liver transplant in 18.2% (n = 85) of patients. Development of bronchiectasis was detected in only 13 patients (2.7%). We determined a 13.64-fold risk of developing bronchiectasis in patients with chronic obstructive pulmonary disease and 10.08-fold risk in patients with pneumonia by multivariate regression analyzes, in which all possible risk factors for the development of bronchiectasis after transplant were evaluated. CONCLUSIONS: The pathophysiology of transplantassociated bronchiectasis has not yet been clarified. Underlying diseases, recurrent pulmonary infections, and potential effects from immunosuppressive drugs may contribute to the pathogenesis of bronchiectasis. Further prospective studies are needed to include long-term health outcomes in transplant patients with and without bronchiectasis.

Relationships between bronchiectasis and time to achieving target trough immunoglobulin G levels in patients with common variable immunodeficiency.

Background: The main treatment of common variable immunodeficiency (CVID) is to maintain immunoglobulin G (IgG) levels within the target range. However, trough IgG levels differ among patients with similar body mass index (BMI) and those receiving the same dose of immunoglobulin replacement therapy (IGRT). A crucial factor that underlies these differences is the presence of extensive bronchiectasis, which is associated with the immunoglobulin salvage pathway. Objective: We compared trough IgG levels in patients with CVID and with and in those without bronchiectasis who had received the same dose of IGRT for 2 years to determine the association of IgG level with infection frequency. Method: This retrospective cohort study included 61 patients with CVID, of whom 21 had bronchiectasis. We reviewed the electronic records for demographic variables, baseline immunoglobulin levels, mean trough IgG levels over 2 years, efficacy levels (trough IgG level - baseline IgG level), the time interval from treatment initiation to achieving the target trough IgG level (700 mg/dL), and the number of infections. Results: The median age of the patients was 39 years (IQR, 27-51), and 29 were women (47.5%). There were no significant differences between the groups in terms of age, age at diagnosis, delay in diagnosis, sex, BMI, IGRT type (subcutaneous or intravenous), and baseline immunoglobulin levels. Trough IgG and efficacy levels were lower (P < 0.001 and P = 0.016, respectively), the time required to achieve the target IgG level was longer in patients with bronchiectasis than in those without bronchiectasis, and this time interval was significantly associated with the infection frequency. Trough IgG and albumin levels were correlated (p = 0.007), with minor differences between the groups (p = 0.04). Conclusion: Bronchiectasis was significantly associated with a longer time to achieve the target IgG levels. These long-term differences between the patients with and those without bronchiectasis have significant clinical implications.

Bronchiectasis in Türkiye: Data from a Multicenter Registry (Turkish Adult Bronchiectasis Database).

Background: Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. Aims: We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. Study Design: A multicenter prospective cohort study. Methods: The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Results: Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research council dyspnea scale score (OR: 1,952; 95% CI: 1,459-2,611), presence of chronic renal failure (OR: 4,172; 95% CI: 1,249-13,938) and use of inhaled steroids (OR: 2,587; 95% CI: 1,098-6,098) were significant risk factors for mortality. Mortality rates were higher in patients with COPD than in those with no COPD (21.7-9.1%, p = 0.016). Patients with bronchiectasis and COPD exhibited more frequent exacerbations, exacerbation-related hospitalizations, and hospitalization in the intensive care unit in the previous year than patients without COPD. Conclusion: This is the first multicenter study of bronchiectasis in Türkiye. The study results will provide important data that can guide the development of health policies in Türkiye on issues such as infection control, vaccination, and the unnecessary use of antibiotics and steroids.

Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study.

BACKGROUND: Epidemiological observational studies have elucidated a correlation between rheumatoid arthritis (RA) and bronchiectasis. However, the causal nature of this association remains ambiguous. To clarify this potential causal linkage, we conducted a two-sample Mendelian randomization (MR) analysis to explore the bidirectional causality between RA and bronchiectasis. METHODS: Summary statistics for RA and bronchiectasis were obtained from the IEU OpenGWAS database We employed various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode, to explore potential causal links between RA and bronchiectasis. Additionally, a series of sensitivity studies, such as Cochran's Q test, MR Egger intercept test, and leave-one-out analysis, were conducted to assess the MR analysis's accuracy further. RESULTS: In the forward MR analysis, the primary analysis indicated that a genetic predisposition to RA correlated with an increased risk of bronchiectasis in European populations (IVW odds ratio (OR): 1.28, 95% confidence interval (CI): 1.20-1.37, p = 1.18E-13). Comparable results were noted in the East Asian subjects (IVW OR: 1.55, 95% CI: 1.30-1.34, p = 8.33E-07). The OR estimates from the other four methods were consistent with those obtained from the IVW method. Sensitivity analysis detected no evidence of horizontal pleiotropy or heterogeneity. Conversely, in the reverse MR analysis, we found no evidence to support a genetic causality between bronchiectasis and RA in either European or East Asian populations. CONCLUSION: This study indicates that genetic predisposition to RA correlates with a heightened risk of bronchiectasis in both European and East Asian populations. These results imply that routine screening for bronchiectasis in RA patients could be beneficial, and effective management of RA may contribute to a reduced risk of bronchiectasis. Future research should aim to clarify the underlying mechanisms linking these two conditions.

Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.

Incremental Load Respiratory Muscle Training Improves Respiratory Muscle Strength and Pulmonary Function in Children with Bronchiectasis.

Methods: Participants underwent respiratory muscle training for 24 weeks. The main results were changes in respiratory muscle strength and pulmonary function indices (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), forced expiratory flow 25-75% (FEF25-75%), and maximal midexpiratory flow 75/25 (MMEF75/25)) before, 12 weeks after, and 24 weeks after the intervention. The secondary outcomes were changes in the exercise load and work rate, exercise work, Leicester Cough Questionnaire (LCQ) scale, and Fatigue Severity Scale (FSS). Results: Compared with before the intervention, after 24 weeks of respiratory muscle training, the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were significantly enhanced (P < 0.05), while FVC, FEV1, and PEF were significantly increased (P < 0.01). FEF25-75 and MMEF75/25 values showed significant improvement compared to those before training (P < 0.05). The exercise loading, work, and exercise work rate of expiratory muscle training were significantly improved compared to those before intervention (P < 0.05). The LCQ score increased significantly (P < 0.001), and the FSS score decreased significantly (P < 0.001). Conclusion: Incremental load respiratory muscle training effectively improved children's lung function over the long term, improved the strength of their inspiratory and expiratory muscles, and improved their quality of life.

Association between bronchiectasis exacerbations and longitudinal changes in FEV1 in patients from the US bronchiectasis and NTM research registry.

BACKGROUND: This study aimed to evaluate the association between the number of non-cystic fibrosis bronchiectasis (bronchiectasis) exacerbations during baseline and follow-up (objective 1) and to identify longitudinal changes in FEV1 associated with exacerbation frequency (objective 2). METHODS: This was a retrospective cohort study of adult patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry September 2008 to March 2020. Objective 1 outcome was association between exacerbations during baseline (24 months) and 0-to-24 month and 24-to-48 month follow-up windows. Objective 2 outcomes were change in FEV1 and FEV1 % predicted over 24 months stratified by baseline exacerbation frequency. RESULTS: Objective 1 cohort (N = 520) baseline frequency of any exacerbations was 59.2%. Overall, 71.4% and 75.0% of patients with ≥1 baseline exacerbations had ≥1 exacerbations during the 0-to-24 and 24-to-48 month follow-ups. Having ≥1 exacerbation during baseline was significantly associated with ≥1 exacerbation during the 0-to-24 month (P = 0.0085) and 24-to-48 month follow-ups (P=<0.0001). Objective 2 cohort (N = 431) baseline FEV1 was significantly lower in patients who had more exacerbations; however, decline in FEV1 from baseline was not significantly different between patients with 0, 1, and ≥2 exacerbations. In patients with more baseline exacerbations, FEV1 % predicted was significantly lower at baseline (P < 0.0001) and at 12 (P = 0.0002) and 24 month follow-ups (P < 0.0001). CONCLUSIONS: Patients with frequent bronchiectasis exacerbations may be more likely than those with less frequent exacerbations to experience disease progression based on future exacerbation frequency and lower FEV1 at baseline, although FEV1 decline may not differ by baseline exacerbation frequency.

Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

Effects of high-flow nasal cannula oxygen therapy in bronchiectasis and hypercapnia: a retrospective observational study.

BACKGROUND: The effectiveness of high-flow nasal cannula (HFNC) therapy in patients with bronchiectasis experiencing hypercapnia remains unclear. Our aim was to retrospectively analyze the short-term outcomes of HFNC therapy in such patients, and to further explore the predictors of HFNC treatment failure in this particular patient population. METHODS: A retrospective review was conducted on patients with bronchiectasis who received HFNC (n = 70) for hypercapnia (arterial partial pressure of carbon dioxide, PaCO2 ≥ 45 mmHg) between September 2019 and September 2023. RESULTS: In the study population, 30% of patients presented with acidemia (arterial pH < 7.35) at baseline. Within 24 h of HFNC treatment, there was a significant reduction in PaCO2 levels by a mean of 4.0 ± 12.7 mmHg (95% CI -7.0 to -1.0 mmHg). Concurrently, arterial pH showed a statistically significant increase with a mean change of 0.03 ± 0.06 (95% CI 0.01 to 0.04). The overall hospital mortality rate in our study was 17.5%. The median length of hospital stay was 11.0 days (interquartile range [IQR] 8.0 to 16.0 days). Sub-analysis revealed no statistically significant differences in hospital mortality (19.0% vs. 20.4%, p = 0.896), length of hospital stay (median 14.0 days [IQR 9.0 to 18.0 days] vs. 10.0 days [IQR 7.0 to 16.0 days], p = 0.117) and duration of HFNC application (median 5.0 days [IQR 2.0 to 8.5 days] vs. 6.0 days [IQR 4.9 to 9.5 days], p = 0.076) between the acidemia group and the non-acidemia group (arterial pH ≥ 7.35). However, more patients in the non-acidemia group had do-not-intubate orders. The overall treatment failure rate for HFNC was 28.6%. Logistic regression analysis identified the APACHE II score (OR 1.24 per point) as the independent predictor of HFNC failure. CONCLUSIONS: In patients with bronchiectasis and hypercapnia, HFNC as an initial respiratory support can effectively reduce PaCO2 level within 24 h of treatment. A high APACHE II score has emerged as a prognostic indicator for HFNC treatment failure. These observations highlight randomized controlled trials to meticulously evaluate the efficacy of HFNC in this specific population.

Comparative microbiome analysis in cystic fibrosis and non-cystic fibrosis bronchiectasis.

BACKGROUND: Bronchiectasis is a condition characterized by abnormal and irreversible bronchial dilation resulting from lung tissue damage and can be categorized into two main groups: cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Both diseases are marked by recurrent infections, inflammatory exacerbations, and lung damage. Given that infections are the primary drivers of disease progression, characterization of the respiratory microbiome can shed light on compositional alterations and susceptibility to antimicrobial drugs in these cases compared to healthy individuals. METHODS: To assess the microbiota in the two studied diseases, 35 subjects were recruited, comprising 10 NCFB and 13 CF patients and 12 healthy individuals. Nasopharyngeal swabs and induced sputum were collected, and total DNA was extracted. The DNA was then sequenced by the shotgun method and evaluated using the SqueezeMeta pipeline and R. RESULTS: We observed reduced species diversity in both disease cohorts, along with distinct microbial compositions and profiles of antimicrobial resistance genes, compared to healthy individuals. The nasopharynx exhibited a consistent microbiota composition across all cohorts. Enrichment of members of the Burkholderiaceae family and an increased Firmicutes/Bacteroidetes ratio in the CF cohort emerged as key distinguishing factors compared to NCFB group. Staphylococcus aureus and Prevotella shahii also presented differential abundance in the CF and NCFB cohorts, respectively, in the lower respiratory tract. Considering antimicrobial resistance, a high number of genes related to antibiotic efflux were detected in both disease groups, which correlated with the patient's clinical data. CONCLUSIONS: Bronchiectasis is associated with reduced microbial diversity and a shift in microbial and resistome composition compared to healthy subjects. Despite some similarities, CF and NCFB present significant differences in microbiome composition and antimicrobial resistance profiles, suggesting the need for customized management strategies for each disease.

Phenotype and Clinicoradiological Differences in Multifocal and Focal Bronchiectasis.

Introduction: Bronchiectasis is a chronic progressive respiratory disease characterized by permanent dilatation of the bronchi. It is a complex condition with numerous different etiologies, co-morbidities, and a heterogeneous presentation. As we know, there is a lack of studies that describe the differences and compare the characteristics between focal and multifocal bronchiectasis. The aim of this study is to identify differences in clinical characteristics presentation, severity or distribution in focal and multifocal bronchiectasis, and prognostic implications. Methods: 126 patients with computed tomography (CT)-verified bronchiectasis were enrolled. Baseline characteristics that included age, sex, smoking history, and respiratory symptoms were recorded, with special attention paid to hemoptysis appearance, body mass index, and comorbidities. The type of bronchiectasis determined by CT scan and the modified Reiff scores indicating radiological severity were recorded. Patients were divided in two groups (I is focal and II is multifocal). Results: There were no statistically significant differences in age, smoking status, comorbidity, and BMI between the two groups. Multifocality was associated with a significantly higher proportion of females (p = 0.014), the rate of hemoptysis (p = 0.023), and the number of hospitalizations, but not of exacerbations and prevalence of immunodeficiency (p = 0.049). Significantly, a high number of subjects with multifocality had bronchiectasis of moderate severity, and post-infective and asthma-associated phenotypes were the dominant in this group. Unexpectedly, the cystic and varicose radiological phenotype (which need more time to develop) were more dominant in the focal group. The cylindrical phenotype was equally observed in the multifocal and focal groups. Conclusions: Our study suggests that multifocality is not related to age, number of exacerbations, or radiological phenotype, but it seems to be associated with the clinical post-infective phenotype, immunodeficiency, frequent hospitalizations, and severity. Thus, the presence of multifocal bronchiectasis may act as a biomarker of severity and poor outcomes in these patients.

The Rationale, Evidence, and Adaptations to Pulmonary Rehabilitation for Chronic Respiratory Diseases Other Than COPD.

Over the last 3 decades, pulmonary rehabilitation (PR) has become an integral part of the management of COPD. Many other chronic respiratory diseases have similar systemic manifestations including skeletal muscle impairment, commonly through deconditioning, and may benefit from PR. However, whereas many programs may accept patients with other respiratory diseases, the program may need several adaptations to optimally manage patients. This article uses the examples of interstitial lung disease including idiopathic pulmonary fibrosis, bronchiectasis, pulmonary hypertension, post lung transplantation, and post-COVID condition to highlight exemplar clinical problems. In addition, the rationale and latest evidence for PR are described alongside the adaptations to the program, including education needs of the delivery team and close integrated care with the wider clinical team. Finally, future directions for clinical care and research are discussed.

Effect of pulmonary rehabilitation in patients with post-tuberculosis sequelae with functional limitation.

BACKGROUND: Pulmonary rehabilitation improves dyspnea, functional limitation and quality of life in patients with chronic respiratory disease especially Chronic obstructive pulmonary disease (COPD). Whether Pulmonary rehabilitation (PR) will have similar effect in patients with post-tuberculosis sequelae or not and whether the two morphological variants will respond similarly or not was the purpose of our study. METHODS: Adult patients fulfilling the inclusion criteria of a diagnosis of post-tuberculosis sequelae with functional limitation (modified medical research council [mMRC] grade 1 or more) were recruited over a period of two years. A baseline health assessment in the different domains of health was done at the beginning and repeated just after the completion of the rehabilitation program at 6 weeks. RESULTS: 26 patients completed the PR protocol of our study. Dyspnea improved from an mMRC grade of 1.5 to 0.7 post-PR (p < 0.001). 6MWD increased by 34 meters from a baseline value of 408.6 meters to 442.7 meters post-PR. (p-value 0.3) St. George's Respiratory Questionnaire (SGRQ) symptom score decreased by 13 points, SGRQ activity score decreased by 18 points, SGRQ impact score decreased by 18 and SGRQ total score decreased by 17 points with p-values of 0.037, 0.002, 0.004 and 0.002 for SGRQ symptom score, SGRQ activity score, SGRQ impact score, SGRQ total score respectively. Depression Anxiety Stress Scale (DASS) Stress score decreased by 6.7, DASS Anxiety score decreased by 6.6, and DASS Depression score decreased by 5.5 points. Intergroup comparison revealed both bronchiectasis predominant group and fibrosis predominant group responded similarly to PR. CONCLUSION: PR improved parameters assessing dyspnea, quality of life and mental health indices significantly. Improvement in functional capacity was not statically significant. Both the morphological variants responded similarly to the PR.

[Primary antibody deficiencies and respiratory manifestations in adults].

Primary antibody deficiencies (PAD) are a group of congenital disorders caused by genetic defects that affect the development and function of the body's immune defence mechanisms. Patients with PAD may present with recurrent infections, lymphoproliferation, autoimmune diseases, autoinflammation, or malignancies. Respiratory system manifestations may include bronchiectasis, bronchial asthma, and interstitial lung disease, among others. A comprehensive understanding of PADs will help to distinguish these covert cases from more common respiratory diseases.

Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study.

Background: Previous studies have demonstrated that autoimmune diseases are closely associated with bronchiectasis (BE). However, the causal effects between autoimmune diseases and BE remain elusive. Methods: All summary-level data were obtained from large-scale Genome-Wide Association Studies (GWAS). The univariate Mendelian randomization (UVMR) was utilized to investigate the genetic causal correlation (rg) of 12 autoimmune diseases and bronchiectasis, The Multivariable Mendelian Randomization (MVMR) method was used to explore the effects of the confounding factors. Further investigation was conducted to identify potential intermediate factors using mediation analysis. Finally, the linkage disequilibrium score regression (LDSC) method was used to identify genetic correlations among complex traits. A series of sensitivity analyses was performed to validate the robustness of the results. Results: The LDSC analysis revealed significant genetic correlations between BE and Crohn's disease (CD) (rg = 0.220, P = 0.037), rheumatoid arthritis (RA) (rg = 0.210, P = 0.021), and ulcerative colitis (UC) (rg = 0.247, P = 0.023). However, no genetic correlation was found with other autoimmune diseases (P > 0.05). The results of the primary IVW analysis suggested that for every SD increase in RA, there was a 10.3% increase in the incidence of BE (odds ratio [OR] = 1.103, 95% confidence interval [CI] 1.055-1.154, P = 1.75×10-5, FDR = 5.25×10-5). Furthermore, for every standard deviation (SD) increase in celiac disease (CeD), the incidence of BE reduced by 5.1% (OR = 0.949, 95% CI 0.902-0.999, P = 0.044, FDR = 0.044). We also observed suggestive evidence corresponding to a 3% increase in BE incidence with T1DM (OR = 1.033, 95% CI 1.001-1.066, P = 0.042, FDR = 0.063). Furthermore, MVMR analysis showed that RA was an independent risk factor for BE, whereas mediator MR analysis did not identify any mediating factors. The sensitivity analyses corroborated the robustness of these findings. Conclusion: LDSC analysis revealed significant genetic correlations between several autoimmune diseases and BE, and further MVMR analysis showed that RA is an independent risk factor for BE.