Background Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who ‘failed’ recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. Main text There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa ( Pa ) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. Conclusion Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.

Cough peak flow (CPF) is a useful clinical measurement to assess neuromuscular activity and effective coordination, yet it is rarely used in clinical practice outside of the management of patients with neuromuscular disorders. A CPF of above 160 L/min is required for an effective cough and less than 270 L/min is associated with increased secretion retention and risk of infection. Reduced CPF can be due to a number of mechanisms including reduced respiratory muscle strength, lack of co-ordination of glottic closure and opening, airway obstruction and, age and activity related changes. CPF has been shown to be correlated with other measures of pulmonary function in neuromuscular disorders and in predicting extubation failure. Patients with Parkinson's disease have a reduced CPF even at early stages and dedicated expiratory muscle strength training (EMST) has been shown to be beneficial. Sequential studies in patient with stroke-associated dysphagia reported CPF was correlated with risk of respiratory infection and results of formal swallow assessments. Age-related changes in expiratory muscle strength and lung physiology contribute to increased risk of aspiration and pneumonia. EMST may have a role in healthy adults to improve muscle strength and effective cough, potentially reducing risk of respiratory tract infections even in the absence of disease. CPF has potential to be extremely useful in clinical practice in a wide spectrum of diseases. In particular, studies in patients with frequent exacerbations of COPD and recurrent pneumonia are currently lacking and would be of benefit to explore the relationship between ineffective cough and recurrent infection.

In the early twentieth century, bronchiectasis (BE) was not a disease seen in the elderly population as life expectancy was usually < 40 years. A century on, however, and this is now a disease much more prevalent in the elderly and as patients live longer, this trend will almost certainly continue. Why is this so? (1) BE is irreversible and often worsens with advancing years and (2) aetiologies associated with new-onset BE in the elderly are strongly related to the ageing process itself—namely gastro-oesophageal reflux disease (GORD), immunosenescence, cancer and inflammatory diseases, oral sepsis, aspiration of food and liquid into the respiratory tract and development of pulmonary fibrosis. BE can also complicate chronic airway diseases such as COPD, which becomes more prevalent with age, and is associated with more rapid disease progression and a higher mortality. In both the BSI and FACED BE mortality prediction scores, age is an independent risk factor for death. At present, GORD and aspiration are considered to be the primary cause of few cases of BE. There is however a lot of data supporting the role of GORD and the severity of BE and its prognosis. Similarly, the data implicating aspiration in elderly patients as a major risk factor for the development of community-acquired pneumonia is overwhelming yet it is rarely looked for and the subsequent bronchiectasis is usually labelled as post-infective rather than due to aspiration. In older patients with recurrent chest infections and/or chronic cough and sputum, it is, therefore, critical to think of BE and investigate appropriately including testing for GORD and aspiration. Treatment involves attenuation of risk wherever possible and the twin pillars of sputum clearance and judicious use of antibiotics.

We report a 67 year old lady with Rheumatoid Arthritis (RA) and mild bronchiectasis (BE) whose treatment was escalated to Rituximab. Nine months after commencing Rituximab her lung sepsis worsened dramatically with repeated hospitalization, new sputum isolation of Stenotrophomonas maltophilia and Pseudomonas aeruginosa and marked radiological deterioration in BE. She was found to have a low serum IgG and IgM levels almost certainly as a complication of Rituximab. Immunoglobulin replacement therapy was instituted and her clinical status has slowly improved.

Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has not yet been fully elucidated and a greater understanding of the pathophysiology of the interaction and potential therapies is required. This review explores the underlying pathophysiology of GORD, its clinical presentation, risk factors, commonly applied diagnostic tools, and a detailed synthesis of original articles evaluating the prevalence of GORD, its influence on disease severity and current management strategies within the context of bronchiectasis. The prevalence of GORD in bronchiectasis ranges from 26% to 75%. Patients with co-existing bronchiectasis and GORD were found to have an increased mortality and increased bronchiectasis severity, manifest by increased symptoms, exacerbations, hospitalisations, radiological extent and chronic infection, with reduced pulmonary function and quality of life. The pathogenic role of Helicobacter pylori infection in bronchiectasis, perhaps via aspiration of gastric contents, also warrants further investigation. Our index of suspicion for GORD should remain high across the spectrum of disease severity in bronchiectasis. Identifying GORD in bronchiectasis patients may have important therapeutic and prognostic implications, although clinical trial evidence that treatment targeted at GORD can improve outcomes in bronchiectasis is currently lacking.

BACKGROUND: This study assessed if bronchiectasis (BR) and rheumatoid arthritis (RA), when manifesting as an overlap syndrome (BROS), were associated with worse outcomes than other BR etiologies applying the Bronchiectasis Severity Index (BSI).METHODS: Data were collected from the BSI databases of 1,716 adult patients with BR across six centers: Edinburgh, United Kingdom (608 patients); Dundee, United Kingdom (n = 286); Leuven, Belgium (n = 253); Monza, Italy (n = 201); Galway, Ireland (n = 242); and Newcastle, United Kingdom (n = 126). Patients were categorized as having BROS (those with RA and BR without interstitial lung disease), idiopathic BR, bronchiectasis-COPD overlap syndrome (BCOS), and "other" BR etiologies. Mortality rates, hospitalization, and exacerbation frequency were recorded.RESULTS: A total of 147 patients with BROS (8.5% of the cohort) were identified. There was a statistically significant relationship between BROS and mortality, although this relationship was not associated with higher rates of BR exacerbations or BR-related hospitalizations. The mortality rate over a mean of 48 months was 9.3% for idiopathic BR, 8.6% in patients with other causes of BR, 18% for RA, and 28.5% for BCOS. Mortality was statistically higher in patients with BROS and BCOS compared with those with all other etiologies. The BSI scores were statistically but not clinically significantly higher in those with BROS compared with those with idiopathic BR (BSI mean, 7.7 vs 7.1, respectively; P < .05). Patients with BCOS had significantly higher BSI scores (mean, 10.4), Pseudomonas aeruginosa colonization rates (24%), and previous hospitalization rates (58%).CONCLUSIONS: Both the BROS and BCOS groups have an excess of mortality. The mechanisms for this finding may be complex, but these data emphasize that these subgroups require additional study to understand this excess mortality.

Introduction Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality.Methods We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies.Results The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline.Conclusion The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.

Background: This study aims to examine the predictive and prognostic implications of C-reactive protein (CRP) and clinically relevant baseline variables in determining treatment indication and disease progression in a large clinical cohort of patients with stable sarcoidosis. Methods: A retrospective observational study of 328 sarcoidosis patients attending a regional tertiary referral centre over a 26-year period was performed. Clinical, biochemical, radiological and physiological data were analysed according to a clinically relevant dichotomous cutpoint of CRP. Multiple models of logistic regression were used to determine independent predictors of outcome as defined by indication for treatment with corticosteroids, radiological deterioration and physiological progression. Results: 328/409 (80.2%) sarcoidosis patients had baseline serum CRP measured and were suitable for inclusion. Baseline CRP was elevated in 154 (47%). 178 (54.3%) were prescribed corticosteroid treatment during the disease course. Physiological deterioration was demonstrated in 48 (14.6%) patients and radiological progression in 59 (17.9%) patients. High baseline CRP was strongly associated with Lofgren's syndrome (p=< 0.001) and reduced FVC% predicted (p=0.012). High CRP was found to be a negative predictor of radiological progression (p=0.046). In a sub-analyses of patients without Lofgren's syndrome (n=223), patients with high baseline CRP were almost twice as likely to receive corticosteroid treatment, OR 1.89 (95% CI 1.04-3.55). Low baseline DLCO% independently predicted the need for corticosteroid treatment (p=< 0.001) and physiological decline (p=0.045). Conclusions: Elevated baseline CRP in sarcoidosis is associated with a good prognosis and is a negative predictive indicator of radiological progression. In patients without Lofgren's syndrome, high CRP and low DLCO% at presentation may identify a subset of patients more likely to develop physiological progression who may benefit from early systemic treatment.

Background Few studies have assessed the role of lung diffusing capacity (DLCO%) in bronchiectasis. We sought to examine the relationship between DLCO% and clinical and radiological variables in a well-defined population of bronchiectasis patients to determine its potential prognostic significance and compare with FEV1%. Methods Of 312 consecutive bronchiectasis patients attending our institution over a 3-year period, 204 patients were suitable for study inclusion. Exclusion criteria consisted of patients with cystic fibrosis or traction bronchiectasis, patients with missing data and patients with absent radiological evidence of bronchiectasis on independent expert thoracic radiologist review. Univariate analyses was performed using Pearson’s correlation. Backwards stepwise logistic regression analysis was subsequently performed to determine independent associations of DLCO% and FEV1%. Results DLCO% strongly correlated with all measured lung function parameters FEV1%, FVC%, FEF 25–75% and FEV1/FVC ratio (all p < 0.001). Negative correlations were noted with age at diagnosis (p = 0.047), body mass index (p < 0.001) and number of comorbidities (p = 0.002). Significant symptom associations included SOB (p = 0.001) and fatigue (p < 0.001). Reduced DLCO% was associated with higher MRCD scores (p < 0.001), higher number of hospitalisations on follow up (p = 0.015), higher BSI scores (p < 0.001) and increased mortality (p = 0.028). No correlations were noted with gender, smoking history, aetiology or bacterial colonisation of any form. Reduced DLCO% was associated with increased number of lobes (p = 0.004), and higher total Reiff and modified Bhalla HRCT scores (p = 0.001 and p < 0.001 respectively). The modified Bhalla was excluded from stepwise regression as unavailable in most clinical settings. Backwards elimination showed DLCO% to be significant in predicting BSI (p < 0.001), number of lobes (0.017) and mortality (p = 0.028). Comparatively, backwards stepwise regression of FEV1% showed significance in predicting BSI (p < 0.001), number of hospitalisations on follow up (p = 0.008), and mortality (p = 0.024). Separate regression models of DLCO% and FEV1% using modified Bhalla components as cofactors showed DLCO% to be associated with disease extent (p = 0.002), bronchial wall thickness (p < 0.001), bronchial wall dilatation (p < 0.001) and reduced parenchymal attenuation (p = 0.015); FEV1% was associated with bronchial wall dilatation only (p < 0.001). Conclusion DLCO% predicts radiological disease, disease severity and mortality in bronchiectasis, independently of aetiology, and may identify patients with advanced disease who could benefit from intensive management.

Significant breathlessness on bending forward (bendopnoea) is often reported by COPD patients and, in our experience, is sometimes the sentinel symptom of their COPD. To date, there is a paucity of research into this disabling symptom. Methods: We conducted a prospective observational study to examine the prevalence and potential mechanisms of bendopnoea in COPD patients undergoing pulmonary rehabilitation. Demographic, clinical and functional data were obtained including pulmonary function tests, exercise capacity and quality of life. Bendopnoea was assessed by measuring the severity of shortness of breath on bending forward at the waist for up to 30 seconds. BORG score, oxygen saturations and blood pressure measurements were obtained before and after this manoeuvre and, if symptomatic, the time taken for measured parameters to return to baseline values was recorded. Results: 41 patients were assessed, of whom, 23 (56%) patients had objective bendopnoea. Significant associations with comorbidities (p=0.01), reduced lung function (lower FEV1%, RV% and DLCO%, p=0.01, 0.02 and <0.001 respectively) and poorer QoL (p=0.03) were noted with significant trends towards an increased waist to hip ratio (p=0.08) and clinical evidence of right heart failure (p=0.06). There were no associations with age, BMI, respiratory symptoms, exacerbation frequency, MRCD score, HADS score, exercise capacity or baseline oxygen saturation. Conclusion: The mechanism of bendopnoea in COPD has yet to be determined but poor baseline airways disease and possibly emphysema, as judged by lower DLCO, appear to be important mechanisms, with the presence of bendopnoea perhaps a signal of disease progression in these patients.

Use of pulse oximetry to measure oxygen saturation is a critical component in the assessment and monitoring of hospitalized patients.1 There is evidence, however, that pulse oximetry is seldom employed when assessing acute oxygenation status in the community.2 In primary care, pulse oximetry has been shown to be helpful in identifying children with serious infections,3 in stratifying acute severe asthma as recommended by the 2015 global initiative for asthma (GINA) guidelines,4 and in refining the acute treatment of patients with asthma and chronic obstructive pulmonary disease (COPD).5 To our knowledge, there is no previous study documenting usage and detailed clinical …

Introduction: Quantifying the impact of Pseudomonas aeruginosa (PA) on prognosis in bronchiectasis is essential to guide the use of new therapies and to determine the role of eradication therapies. Methods: Data from 21 cohorts, including unpublished cohorts, of patients with bronchiectasis from Europe, Asia and Australia were subject to random effects meta-analysis comparing outcomes in patients colonised with PA compared to those without. Quality of life was assessed with the St.George9s Respiratory Questionnaire (SGRQ). Results: We included data for 2136 patients. The overall prevalence of PA was 23%. Patients with PA had 3 fold increase risk of death (OR 2.95 95% CI 1.98-4.41, p<0.0001), increased risk of hospital admissions (OR 5.91 95% CI 2.54-13.8, p<0.0001), a mean increase of 1 exacerbation per year (p<0.0001), worse quality of life (mean difference 18 points using the SGRQ, p<0.0001), and lower lung function (FEV1 -15% 95% CI 11.3-18.7% and FVC -9.4 9% CI 4.5-14.3, both p<0.0001) compared to patients without PA. Data were highly consistent for these end-points and heterogeneity was at an acceptable level. There was limited and inconsistent data available for the effect of PA on lung function decline Conclusion: PA colonisation is consistently associated with increased mortality, exacerbations and healthcare utilisation and poorer quality of life, confirming the clinical significance of colonisation. This analysis provides the most precise estimates to date on the impact of PA on clinical outcomes in bronchiectasis.

Background: Symptomatic gastro-oesophageal reflux disease (GORD) has been associated with increased exacerbations and reduced quality of life in bronchiectasis (BR). We aimed to evaluate the prevalence of a BR-GORD phenotype, utilising the multi-domain Bronchiectasis Severity Index (BSI), to determine associations with disease severity and mortality. Methods: A retrospective cohort study in 212 consecutive BR patients attending our institution over a 2-year period was performed. A diagnosis of GORD was based on standardised definitions following full review of electronic records, review of prescriptions and investigator definitions. Results: 72 (19.8%) BR patients were confirmed to have co-existent GORD treated with proton pump inhibitors. These patients were predominantly male, older and with higher BMIs than their counterparts (p=<0.001, 0.002 and 0.038 respectively). Significant symptom associations included cough (p=0.002), daily sputum production (p=0.040) and wheeze (p<0.001). Exacerbation frequency (p=0.011), number of hospitalisations (p=0.022), no. of lobes affected (p<0.001), cystic disease (p=0.006), Pseudomonas colonisation (p=0.017) and no. of microbes cultured on follow up (p=0.008) were significantly higher in the BR-GORD group leading to higher BSI scores (p=0.004) and increased mortality (p=0.026). Logistic regression analysis showed BSI (OR 2.2, 95% CI 1.1-6.7) and mortality (OR 2.5, 95% CI 1.1-7.8) to be independently associated with the BR-GORD phenotype. Conclusion: BR-GORD patients have an increased disease severity and mortality risk compared with BR patients without GORD. Increased recognition of this BR-GORD phenotype and its potential for targeted therapy is needed.