Predicting mortality in non-cystic fibrosis bronchiectasis patients using distance-saturation product.

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality. METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality. RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831). CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

Serum hepatocyte growth factor as a predictor of disease severity and future exacerbations in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Serum biomarkers associated with the severity of non-cystic fibrosis (CF) bronchiectasis are insufficient. This study determined the association of serum hepatocyte growth factor (HGF), osteopontin, and pentraxin-3 levels with disease severity and exacerbation in patients with non-CF bronchiectasis. METHODS: Serum levels of HGF, osteopontin, and pentraxin-3 were measured in patients with clinically stable non-CF bronchiectasis (n = 61). The correlation between the biomarkers and bronchiectasis severity index (BSI) and FACED score was assessed using univariate and multivariate linear regression analyses. Predictive variables associated with exacerbation were analyzed using a Cox proportional hazards model and the time to first exacerbation in high and low HGF groups during the observation period was compared using Kaplan-Meier survival curves. RESULTS: The BSI showed significant correlation with HGF (r = 0.423; p = 0.001) and pentraxin-3 (r = 0.316; p = 0.013). The FACED score was significantly correlated with HGF (r = 0.406; p = 0.001). Univariate and multivariate linear regression analysis revealed that serum level of HGF was independently associated with both scoring systems. The high HGF group showed a significantly shorter time to first exacerbation (Log-rank test, p = 0.014). Multivariate Cox proportional hazards regression analysis revealed that high serum HGF level and colonization with non-pseudomonas organisms were independent predictors of future exacerbations (HR 2.364; p = 0.024 and HR 2.438; p = 0.020, respectively). CONCLUSION: Serum level of HGF is a potential biomarker that is closely associated with disease severity and future risk of exacerbations in patients with non-CF bronchiectasis.

The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study.

BACKGROUND: Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. METHODS: We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3-V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. FINDINGS: Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33-7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07-2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). INTERPRETATION: A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. FUNDING: British Lung Foundation and European Respiratory Society EMBARC2 consortium.

Exercise training for bronchiectasis.

BACKGROUND: Bronchiectasis is characterised by excessive sputum production, chronic cough, and acute exacerbations and is associated with symptoms of dyspnoea and fatigue, which reduce exercise tolerance and impair quality of life. Exercise training in isolation or in conjunction with other interventions is beneficial for people with other respiratory diseases, but its effects in bronchiectasis have not been well established. OBJECTIVES: To determine effects of exercise training compared to usual care on exercise tolerance (primary outcome), quality of life (primary outcome), incidence of acute exacerbation and hospitalisation, respiratory and mental health symptoms, physical function, mortality, and adverse events in people with stable or acute exacerbation of bronchiectasis. SEARCH METHODS: We identified trials from the Cochrane Airways Specialised Register, ClinicalTrials.gov, and the World Health Organization trials portal, from their inception to October 2020. We reviewed respiratory conference abstracts and reference lists of all primary studies and review articles for additional references. SELECTION CRITERIA: We included randomised controlled trials in which exercise training of at least four weeks' duration (or eight sessions) was compared to usual care for people with stable bronchiectasis or experiencing an acute exacerbation. Co-interventions with exercise training including education, respiratory muscle training, and airway clearance therapy were permitted if also applied as part of usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected trials for inclusion, extracted outcome data, and assessed risk of bias. We contacted study authors for missing data. We calculated mean differences (MDs) using a random-effects model. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included six studies, two of which were published as abstracts, with a total of 275 participants. Five studies were undertaken with people with clinically stable bronchiectasis, and one pilot study was undertaken post acute exacerbation. All studies included co-interventions such as instructions for airway clearance therapy and/or breathing strategies, provision of an educational booklet, and delivery of educational sessions. The duration of training ranged from six to eight weeks, with a mix of supervised and unsupervised sessions conducted in the outpatient or home setting. No studies of children were included in the review; however we identified two studies as currently ongoing. No data were available regarding physical activity levels or adverse events. For people with stable bronchiectasis, evidence suggests that exercise training compared to usual care improves functional exercise tolerance as measured by the incremental shuttle walk distance, with a mean difference (MD) between groups of 87 metres (95% confidence interval (CI) 43 to 132 metres; 4 studies, 161 participants; low-certainty evidence). Evidence also suggests that exercise training improves six-minute walk distance (6MWD) (MD between groups of 42 metres, 95% CI 22 to 62; 1 study, 76 participants; low-certainty evidence). The magnitude of these observed mean changes appears clinically relevant as they exceed minimal clinically important difference (MCID) thresholds for people with chronic lung disease. Evidence suggests that quality of life improves following exercise training according to St George's Respiratory Questionnaire (SGRQ) total score (MD -9.62 points, 95% CI -15.67 to -3.56 points; 3 studies, 160 participants; low-certainty evidence), which exceeds the MCID of 4 points for this outcome. A reduction in dyspnoea (MD 1.0 points, 95% CI 0.47 to 1.53; 1 study, 76 participants) and fatigue (MD 1.51 points, 95% CI 0.80 to 2.22 points; 1 study, 76 participants) was observed following exercise training according to these domains of the Chronic Respiratory Disease Questionnaire. However, there was no change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ) (MD -0.09 points, 95% CI -0.98 to 0.80 points; 2 studies, 103 participants; moderate-certainty evidence), nor in anxiety or depression. Two studies reported longer-term outcomes up to 12 months after intervention completion; however exercise training did not appear to improve exercise capacity or quality of life more than usual care. Exercise training reduced the number of acute exacerbations of bronchiectasis over 12 months in people with stable bronchiectasis (odds ratio 0.26, 95% CI 0.08 to 0.81; 1 study, 55 participants). After an acute exacerbation of bronchiectasis, data from a single study (N = 27) suggest that exercise training compared to usual care confers little to no effect on exercise capacity (MD 11 metres, 95% CI -27 to 49 metres; low-certainty evidence), SGRQ total score (MD 6.34 points, 95%CI -17.08 to 29.76 points), or LCQ score (MD -0.08 points, 95% CI -0.94 to 0.78 points; low-certainty evidence) and does not reduce the time to first exacerbation (hazard ratio 0.83, 95% CI 0.31 to 2.22). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence suggesting improvement in functional exercise capacity and quality of life immediately following exercise training in people with stable bronchiectasis; however the effects of exercise training on cough-related quality of life and psychological symptoms appear to be minimal. Due to inadequate reporting of methods, small study numbers, and variation between study findings, evidence is of very low to moderate certainty. Limited evidence is available to show longer-term effects of exercise training on these outcomes.

Utility of Bronchiectasis severity index (BSI) as prognostic tool in patients with post tubercular bronchiectasis: An experience from a tertiary care hospital in North India.

BACKGROUND: Bronchiectasis severity Index (BSI) score which predicts the severity of the disease along with future exacerbations and mortality rate has been well validated in European patients; however there is paucity of data evaluating its validity in Indian patients. The authors therefore decided to evaluate the utility of BSI to predict exacerbations and mortality rate in patients with post tubercular bronchiectasis presenting to our facility. METHODS: The study was a retrospective observational study done in patients with bronchiectasis secondary to tuberculosis. These patients were followed up for 4 years. BSI was calculated from different variables and descriptive statistics along with regression analysis were used to evaluate utility of BSI. RESULTS: A total of 48 patients of post tubercular bronchiectasis were included in the study. Majority of our patients belonged to severe bronchiectasis group seen in 23 patients (48%) while those with mild and moderate bronchiectasis were seen in 13 (27%) and 12 (25%) patients respectively. The exacerbation rate in mild group was comparable to the predicted BSI exacerbation at 1 year while the predicted and observed rates were statistically significant for moderate and severe bronchiectasis group (p value < 0.05). Mortality rates at 1 year were comparable in all the groups of bronchiectasis while it was comparable only in mild and moderate group bronchiectasis at 4 years. CONCLUSION: Bronchiectasis severity index seems to predict mortality at 1 year in post tuberculosis bronchiectasis. However, it under predicts 1 year and 4 year exacerbation rates. Hence BSI may not be useful as a prognostic tool in Indian patients with bronchiectasis. Larger multi-centred studies may be required to further evaluate the clinical utility of BSI among Indian population.

Increased mortality in patients with non cystic fibrosis bronchiectasis with respiratory comorbidities.

There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005-2015 data from the Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P < 0.001). Mortality risk was 1.15-fold greater in the bronchiectasis cohort than in the matched cohort (95% confidence interval [CI] 1.09-1.22); mortality was greatest among elderly patients (HR = 1.17, 95% CI 1.10-1.25) and men (HR = 1.19, 95% CI 1.10-1.29). Comorbidities over the study period significantly increased the risk of death in the bronchiectasis cohort relative to the matched cohort: asthma (adjusted HR = 1.20, 95% CI 1.11-1.30), chronic obstructive pulmonary disease (adjusted HR = 1.24, 95% CI 1.15-1.34), pneumonia (adjusted HR = 1.50, 95% CI 1.39-1.63), lung cancer (adjusted HR = 1.85, 95% CI 1.61-2.12), and cardiovascular disease (adjusted HR = 1.34, 95% CI 1.23-1.45). In contrast, there were no significant differences in the risk of death in patients without bronchiectasis-related comorbidities and the matched cohort, except in the case of non-tuberculous mycobacterial infection. In conclusion, all-cause mortality was higher in patients with bronchiectasis cohort than those without bronchiectasis, especially in elderly patients and men. Comorbidities over the study period played a major role in increasing mortality in patients with bronchiectasis relative to those without bronchiectasis.

The contribution of Pseudomonas aeruginosa infection to clinical outcomes in bronchiectasis: a prospective cohort study.

OBJECTIVES: The impact of Pseudomonas aeruginosa on the prognosis of bronchiectasis remains controversial. This study aimed to explore the prognostic value of P. aeruginosa in adult patients with bronchiectasis in central-southern China. PATIENTS AND METHODS: This prospective cohort study enrolled 1,234 patients with bronchiectasis between 2013 and 2019. The independent impact of P. aeruginosa on all-cause mortality, annual exacerbations, and hospitalizations was assessed. RESULTS: P. aeruginosa was isolated from 244 patients (19.8%). A total of 188 patients died over a follow-up period of 16 (1-36) months. Patients with P. aeruginosa had a longer disease course, poorer lung function, more lung lobe involvement, and more severe Bronchiectasis Severity Index (BSI) stage than those without P. aeruginosa. The independent impact of P. aeruginosa was observed on frequent hospitalizations but not on mortality and frequent exacerbations. Moderate- or high-risk comorbidities increased the risk of mortality (hazard ratio [HR]: 1.93, 95% confidence interval [CI]: 1.26-2.95), and this effect was magnified by the presence of P. aeruginosa (HR: 2.11, 95% CI: 1.28-3.48). CONCLUSIONS: P. aeruginosa infection acts as a marker of disease severity as well as predictor of frequent hospitalizations. P. aeruginosa had no independent effect on all-cause mortality. P. aeruginosa combined with moderate- or high-risk comorbidities posed an increased risk of mortality. The management of comorbidities may be a critical target during the treatment of P. aeruginosa infection in bronchiectasis.KEY MESSAGE:P. aeruginosa increased the risk of frequent hospitalizations; however, it had no independent impact on all-cause mortality.P. aeruginosa combined with moderate- or high-risk comorbidities posed an increased risk of mortality.The management of comorbidities may be a critical target during the treatment of P. aeruginosa infection in bronchiectasis.

Body mass index as a predictor of mortality in bronchiectasis: A nationwide population-based study.

INTRODUCTION: The prognosis of bronchiectasis is not well known. The purpose of this study was to evaluate the association between body mass index (BMI) and mortality in bronchiectasis using a large nationwide population-based cohort. MATERIAL AND METHODS: Using the National Health Insurance Service-Health Screening Cohort in Korea, individuals with bronchiectasis were identified from 2004 to 2006 and monitored for up to 10 years. Mortality in bronchiectasis was analyzed based on a BMI score <18.5 kg/m2 (underweight), 1.85-22.9 kg/m2 (normal weight), 23.0-24.9 kg/m2 (overweight), and >25.0 kg/m2 (obese). RESULTS: A total of 2769 individuals with bronchiectasis were included. The underweight, normal weight, overweight, and obese accounted for 5.1%, 40.4%, 25.4%, and 29.3% of all patients with bronchiectasis, respectively. Compared to normal weight, underweight in bronchiectasis was associated with increased all-cause mortality (hazard ratio [HR] = 2.60; 95% confidence interval [CI] = 1.92-3.54), while obese was associated with decreased all-cause mortality (HR = 0.71; 95% CI = 0.55-0.93). This relationship between BMI and mortality was more prominent in respiratory disease-related mortality. CONCLUSIONS: BMI is a predictor of mortality in bronchiectasis. Underweight is associated with increased mortality among individuals with bronchiectasis while obese is associated with decreased mortality.

Trend from 2001 to 2015 in the prevalence of bronchiectasis among patients hospitalized for asthma and effect of bronchiectasis on the in-hospital mortality.

OBJECTIVE: We aimed to analyze the prevalence of bronchiectasis among patients hospitalized with asthma and to assess the effect of suffering bronchiectasis on in-hospital mortality (IHM). METHODS: We used the Spanish National Hospital Discharge Database from 2000 to 2015 to evaluate all admissions for asthma exacerbation as the main diagnosis, dividing them according to the presence or absence of associated bronchiectasis. We assessed time trends in the prevalence, clinical characteristics, length of hospital stay, costs, and IHM. RESULTS: Of 342,644 admissions for asthma, 10,377 (3.02%) had bronchiectasis. The prevalence of bronchiectasis increased from 2.16% in 2001 to 4.47% in 2015 (p < 0.001). Compared to patients without bronchiectasis, those with bronchiectasis were more frequently women (77.06% vs. 22.94%, p < 0.001), were older (68.87 ± 15.16 vs. 47.05 ± 30.66 years, p < 0.001) and had more comorbid conditions (Charlson comorbidity index ≥ 2: 9.45% vs. 6.58%, p < 0.001). Pseudomonas (8% vs. 0.66%, p < 0.001), Aspergillus (0.93% vs. 0.15%, p < 0.001), eosinophilia (0.29% vs. 0.17%, p = 0.005) and IHM (2.07% vs. 1.2%, p < 0.001) were more frequent in patients with bronchiectasis. After multivariable adjustments, IHM was not associated with bronchiectasis. The presence of bronchiectasis was associated with a longer length of hospital stay and higher costs. CONCLUSIONS: Admissions for asthma with bronchiectasis have increased over time in Spain. In our investigation, the presence of bronchiectasis was not associated with higher IHM, but it increased the length of hospital stay and costs.

Staphylococcus aureus and its Effects on the Prognosis of Bronchiectasis.

Bronchiectasis, which is an abnormal and irreversible dilation of one or several bronchial segments, causes significant morbidity and impaired quality of life to patients, mainly as the result of recurrent and chronic respiratory infections. Staphylococcus aureus is a microorganism known for its high infectious potential related to the production of molecules with great pathogenic power, such as enzymes, toxins, adhesins, and biofilm, which determine the degree of severity of systemic symptoms and can induce exacerbated immune response. This review highlighted the clinical significance of S. aureus colonization/infection in bronchiectasis patients, since little is known about it, despite its increasing frequency of isolation and potential serious morbidity.

Prognostic performance of the FACED score and bronchiectasis severity index in bronchiectasis: a systematic review and meta-analysis.

BACKGROUND: Bronchiectasis is a multidimensional lung disease characterized by bronchial dilation, chronic inflammation, and infection. The FACED (Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea) score and Bronchiectasis Severity Index (BSI) are used to stratify disease risk and guide clinical practice. This meta-analysis aimed to quantify the accuracy of these two systems for predicting bronchiectasis outcomes. METHODS: PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for relevant studies. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria. Pooled summary estimates, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic curves were constructed, and the area under the curve (AUC) was used to evaluate prognostic performance. RESULTS: We analyzed 17 unique cohorts (6525 participants) from ten studies. FACED scores with a cut-off value ≥ 5 predicted all-cause mortality better than BSI with a cut-off value ≥ 9, based on pooled sensitivity (0.34 vs 0.7), specificity (0.94 vs 0.66), PLR (4.76 vs 2.05), NLR (0.74 vs 0.48), DOR (6.67 vs 5.01), and AUC (0.87 vs 0.75). Both FACED scores with a cut-off value ≥ 5 (AUC = 0.82) and BSI scores with a cut-off value ≥ 5 or 9 (both AUC = 0.80) help to predict hospitalization. CONCLUSIONS: At a cut-off value ≥ 5, FACED scores can reliably predict all-cause mortality and hospitalization, while BSI scores can reliably predict hospitalization with a cut-off of ≥5 or ≥9. Further studies are essential to validate the prognostic performance of these two scores.

Bronchiectasis and increased mortality in patients with corticosteroid-dependent severe asthma: a nationwide population study.

BACKGROUND: Long-term corticosteroid (CS) use is associated with increased mortality in patients with asthma, and comorbid bronchiectasis is also associated with frequent asthma exacerbation and increased healthcare use. However, there is limited information on whether bronchiectasis further increases mortality in patients with CS-dependent asthma. This study examined the impact of bronchiectasis on mortality in patients with CS-dependent asthma. METHODS: A retrospective cohort of patients with CS-dependent asthma ⩾18 years old was established using records from the Korean National Health Insurance Service database from 2005 to 2015. Patients with CS-dependent asthma with and without bronchiectasis were matched by age, sex, type of insurance, and Charlson comorbidity index. We evaluated the hazard ratio (HR) for all-cause mortality in patients with bronchiectasis compared with those without bronchiectasis. RESULTS: The study cohort included 754 patients with CS-dependent asthma with bronchiectasis and 3016 patients with CS-dependent asthma without bronchiectasis. Patients with CS-dependent asthma with bronchiectasis had a higher all-cause mortality than those without bronchiectasis (8429/100,000 versus 6962/100,000 person-years, p < 0.001). The adjusted HR for mortality in patients with CS-dependent asthma with bronchiectasis relative to those without bronchiectasis was 1.33 (95% confidence interval, 1.18-1.50), and the association was primarily significant for respiratory diseases (subdistribution HR = 1.65, 95% confidence interval, 1.42-1.92). CONCLUSIONS: Bronchiectasis further increases all-cause mortality in patients with CS-dependent asthma, a trend that was especially associated with respiratory diseases including chronic obstructive pulmonary disease. Strategies to improve treatment outcomes in patients with CS-dependent asthma with bronchiectasis are urgently needed to improve long-term survival.The reviews of this paper are available via the supplemental material section.

[Bronchiectasis - a review].

Bronchiectasis is a disease that is characterized by permanent bronchial dilation. This can be localized or diffuse in the lungs. The disease can occur at any age and causes cough, sputum production and repeated infections. It is more common in women and incidence increases with age. Bronchiectasis is characterized by repeated episodes of worsening symptoms that are usually caused by respiratory infections. The cause of bronchiectasis can be unknown but it can be caused by respiratory diseases and diseases outside the chest. Examples of such diseases are asthma, chronic obstructive pulmonary disease, rheumatoid arthritis in addition to immune deficiency. Disease profile is therefore different for each patient. Bronchiectasis is diagnosed with computerized tomography of the chest in addition to clinical symptoms. Workup to diagnose other diseases that could be causing it is therefore important. For that detailed history, physical examination and additional investigations are appropriate. Patients with bronchiectasis have decreased health related quality of life and increased mortality. Treatment focuses on treatment of underlying diseases, airway clearance and treatment of infections. Pulmonary rehabilititation is also important. Regular follow-up is important. This is a review on bronchiectasis that is intended for a spectrum of physicians, because bronchiectasis can be seen in primary care, hospitals and out of hospital.

Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis.

OBJECTIVE: To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi). METHODS: A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths. RESULTS: Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041. CONCLUSION: The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.

Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. METHODS: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. RESULTS: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5-1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1-143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09-1.47), respiratory (aHR, 3.49; 95% CI, 2.21-5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33-5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097-0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631-15.736). CONCLUSION: Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.

Lung Transplantation for Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis: A Single-Center Experience.

OBJECTIVES: Lung transplantation is a well-established treatment for selected patients with advanced cystic fibrosis (CF)- and non-cystic fibrosis (non-CF)--related bronchiectasis. Because the number of lung transplants performed for patients with non-CF bronchiectasis is much smaller than for patients with CF, little data is available regarding patient selection, choice of procedure, and outcomes. METHODS: Between November 1997 and December 2013, 42 patients with CF and 33 patients with non-CF bronchiectasis underwent lung transplantation at the Rabin Medical Center, Israel. We analyzed and compared pretransplant evaluation data and short- and long-term results in both groups. RESULTS: Median survival for the CF group in our study was 8.4 years, compared with 7.1 years for the non-CF group (P = .098), similarly to that reported by the International Society for Heart and Lung Transplantation Registry data. The main survival difference between groups was in the early postoperative period. Both groups achieved similar peak forced expiratory volume in 1 second values and had stable lung function at the 3-year follow-up. Biopsy-proven rates of acute cellular rejection were low for both groups. Rates of chronic lung allograft dysfunction development did not differ between CF and non-CF recipients. CONCLUSION: Our institutional experience confirms that lung transplantation is feasible for non-CF bronchiectasis, and results are comparable to our CF cohort. The increased early mortality in this study occurred from 1999 to 2008 and was probably related to surgical techniques used at the time. Overall, 3-year and 5-year survival were comparable with the International Society for Heart and Lung Transplantation Registry data. Non-CF bronchiectasis patients achieved and maintained satisfactory lung function.

Comparative risks of chronic inhaled corticosteroids and macrolides for bronchiectasis.

INTRODUCTION: Non-cystic fibrosis (CF) bronchiectasis ("bronchiectasis") is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory infections in chronic users of inhaled corticosteroids (ICSs) versus macrolide monotherapy. METHODS: We identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models. RESULTS: We identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23-1.57) for hospitalised respiratory infection, 1.56 (95% 1.49-1.64) for acute exacerbation and 1.09 (95% 0.95-1.25) for mortality. INTERPRETATION: Among patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.

Undetectable mannose binding lectin is associated with HRCT proven bronchiectasis in rheumatoid arthritis (RA).

AIM: The aim of this study was to ascertain whether mannose binding lectin deficiency is implicated in coexistent rheumatoid arthritis and bronchiectasis and to determine whether undetectable mannose binding lectin confers poorer long-term survival in coexistent rheumatoid arthritis and bronchiectasis or in rheumatoid arthritis in general. MATERIALS AND METHODS: A retrospective audit was conducted in a rheumatoid arthritis cohort in which mannose binding lectin had been measured by enzyme linked immunosorbent assay from 2007-11. Rheumatoid arthritis patients with physician diagnosed HRCT proven bronchiectasis were recruited during this time and compared to those with uncomplicated rheumatoid arthritis. Survival from disease onset was recorded in October 2018. Kaplan-Meier survival estimates were performed to assess mortality over time in the two groups. Log rank tests were used for equality of survivor functions. RESULTS: The two groups were demographically comparable. A higher frequency of undetectable mannose binding lectin was observed in coexistent rheumatoid arthritis and bronchiectasis (37.5%) compared to uncomplicated rheumatoid arthritis, (8.9%, P = 0.005). Undetectable mannose binding lectin correlated with a strong trend toward poor survival in rheumatoid arthritis overall (P = 0.057). Cox regression analysis however, showed no difference in the hazard ratio for survival between the two groups when corrected for age, gender, prednisolone use ever, rheumatoid factor status and the full range of MBL concentrations. CONCLUSION: In summary, undetectable mannose binding lectin is associated with coexistent rheumatoid arthritis and bronchiectasis and correlates with poor survival in rheumatoid arthritis overall. These findings further implicate immunodeficiency in the genesis of bronchiectasis in rheumatoid arthritis.