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Introduction: A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible. Objective: To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained. Methods: We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV[1] or FEF[25-75]; consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor. Results: There was a significant increase in FEV[1] of median 110 ml (range,-70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up). Conclusions: This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required. [ABSTRACT FROM AUTHOR]

Competing Interests: None declared.

Competing Interests: None declared

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., (© 2022. The Author(s).)

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., (Copyright © 2022. Published by Elsevier Ltd.)

Journal club commentary on the discriminative accuracy of FEV 1 : FVC thresholds for COPD-related hospitalisation and mortality https://bit.ly/3BaWWY7., Competing Interests: Conflict of interest: M.J. McDonnell has nothing to disclose. Conflict of interest: M. Harrison has nothing to disclose. Conflict of interest: R.M. Rutherford has nothing to disclose., (Copyright ©ERS 2021.)

The inter-relationship between chronic respiratory disease and reflux disease in the airway reflux paradigm is extremely complex and remains poorly characterised. Reflux disease is reported to cause or contribute to the severity of a number of respiratory tract diseases including laryngeal disorders, sinusitis, chronic cough, asthma, COPD, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis and bronchiolitis obliterans post lung transplant. It is now appreciated that reflux disease is not simply caused by liquid acid reflux but rather by a variety of chemical refluxates originating from the stomach and duodenum due to a number of different mechanisms. Reflux disease can be challenging to diagnose, particularly proving its role in the causation of direct respiratory epithelial damage. Significant advances in oesophageal assessment and gastric biomarkers have emerged in recent years as our understanding increases. There are a number of treatments available for reflux disease, both medical and surgical, but there is a paucity of large randomised trials to evaluate their efficacy in the setting of chronic respiratory disease. Everyday clinical practice, however, informs us that treatment failure in reflux disease is common. This clinical review summarises associations between reflux disease in the setting of chronic respiratory diseases and examines available evidence regarding potential therapeutic strategies., Competing Interests: Conflict of interest: M.J. McDonnell reports grants from Health Research Board Ireland and the European Respiratory Society during the conduct of the study. Conflict of interest: E.B. Hunt reports grants from University College Cork during the conduct of the study. Conflict of interest: C. Ward has nothing to disclose. Conflict of interest: J.P. Pearson has nothing to disclose. Conflict of interest: D. O'Toole reports grants from Health Research Board Ireland and Science Foundation Ireland during the conduct of the study. Conflict of interest: J.G. Laffey has nothing to disclose. Conflict of interest: D.M. Murphy reports a UCC Translational Research Access Programme Award during the conduct of the study; personal fees and nonfinancial support from AstraZeneca and Novartis, personal fees from Teva, personal fees from Boehringer Ingelheim and GSK, and personal fees and nonfinancial support from Menarini and Bayer, outside the submitted work. Conflict of interest: R.M. Rutherford has nothing to disclose., (Copyright ©ERS 2020.)

Competing Interests: Competing interests: None declared.

Dyspnoea on bending over (bendopnoea) is most commonly associated with systolic heart failure. COPD patients often also complain of bendopnoea but little is known about this symptom in this patient group. We objectively assessed 44 COPD patients attending pulmonary rehabilitation for bendopnoea in a tertiary referral centre to determine the potential mechanism and clinical implications of this symptom. Bendopnoea was assessed by timing the duration of onset to breathlessness on bending forward at the waist for 30 s. BORG score, oxygen saturations and blood pressure measurements were obtained before and after. Of 44 patients (mean age±SD 66.7 ± 8.4 years; 22 male, BMI 28.1 ± 6.4), bendopnoea was present in 23 (52.3%) patients. This was significantly associated with a lower FEV1% (p = 0.02) and TLCO% (<0.001) and higher CAT score (p = 0.03). A strong trend was also noted with higher waist/hip ratio (p = 0.06). There were no associations with age, BMI, oxygen saturation, static lung volumes, exercise capacity or non-invasive haemodynamic markers such as pro-BNP, physiological changes or echocardiography findings., (Copyright © 2019. Published by Elsevier Ltd.)

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., (Copyright © 2018. Published by Elsevier Ltd.)

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described., Objectives: To establish if there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes., Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality., Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV 1 , radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency., Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.

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., (Copyright © 2017 American College of Chest Physicians. All rights reserved.)

Background: Middle-lobe predominant bronchiectasis affecting the right middle-lobe and/or lingula (RMLP) is classically described in asthenic, elderly females with skeletal abnormalities or associated nontuberculous mycobacterial (NTM) infection., Objectives: We aimed to evaluate the frequency and clinical characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed bronchiectasis patients and determine associations with disease severity., Methods: A retrospective observational cross-sectional cohort study of consecutive bronchiectasis patients in our institution was performed. Data were collected on baseline variables, microbiology status, lung function, and radiology according to the modified Bhalla score. Disease severity was assessed using bronchiectasis severity index (BSI) and FACED severity scores., Results: Of 81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20 (24.7%) had RMLP disease. These patients were significantly younger, female, and with lower BMIs than patients with the classical bronchiectasis phenotype (p = 0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum (p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in RMLP patients were significantly lower than their counterparts (both p < 0.001)., Conclusions: The RMLP phenotype is associated with younger patients than classically described in the literature. An increased rate of NTM infection in this phenotype was noted, particularly in females, but much lower than previously described. Lung function and disease severity scores in this patient group are relatively normal, suggesting a milder phenotype in patients with this form of the disease., (© 2017 S. Karger AG, Basel.)

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: Patients with bronchiectasis often have concurrent comorbidities, but the nature, prevalence, and impact of these comorbidities on disease severity and outcome are poorly understood. We aimed to investigate comorbidities in patients with bronchiectasis and establish their prognostic value on disease severity and mortality rate., Methods: An international multicentre cohort analysis of outpatients with bronchiectasis from four European centres followed up for 5 years was done for score derivation. Eligible patients were those with bronchiectasis confirmed by high-resolution CT and a compatible clinical history. Comorbidity diagnoses were based on standardised definitions and were obtained from full review of paper and electronic medical records, prescriptions, and investigator definitions. Weibull parametric survival analysis was used to model the prediction of the 5 year mortality rate to construct the Bronchiectasis Aetiology Comorbidity Index (BACI). We tested the BACI as a predictor of outcomes and explored whether the BACI added further prognostic information when used alongside the Bronchiectasis Severity Index (BSI). The BACI was validated in two independent international cohorts from the UK and Serbia., Findings: Between June 1, 2006, and Nov 22, 2013, 1340 patients with bronchiectasis were screened and 986 patients were analysed. Patients had a median of four comorbidities (IQR 2-6; range 0-20). 13 comorbidities independently predicting mortality rate were integrated into the BACI. The overall hazard ratio for death conferred by a one-point increase in the BACI was 1·18 (95% CI 1·14-1·23; p<0·0001). The BACI predicted 5 year mortality rate, hospital admissions, exacerbations, and health-related quality of life across all BSI risk strata (p<0·0001 for mortality and hospital admissions, p=0·03 for exacerbations, p=0·0008 for quality of life). When used in conjunction with the BSI, the combined model was superior to either model alone (p=0·01 for combined vs BACI; p=0·008 for combined vs BSI)., Interpretation: Multimorbidity is frequent in bronchiectasis and can negatively affect survival. The BACI complements the BSI in the assessment and prediction of mortality and disease outcomes in patients with bronchiectasis., Funding: European Bronchiectasis Network (EMBARC)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: Although bronchiectasis particularly affects people ≥65 years of age, data describing clinical characteristics of the disease in this population are lacking. This study aimed at evaluating bronchiectasis features in older adults and elderly, along with their clinical outcomes., Methods: This was a secondary analysis of six European databases of prospectively enrolled adult outpatients with bronchiectasis. Bronchiectasis characteristics were compared across three study groups: younger adults (18-65 years), older adults (66-75 years), and elderly (and ≥76 years). 3-year mortality was the primary study outcome., Results: Among 1258 patients enrolled (median age: 66 years; 42.5% males), 50.9% were ≥65 years and 19.1 ≥ 75 years old. Elderly patients were more comorbid, had worse quality of life and died more frequently than the others. Differences were detected among the three study groups with regard to neither the etiology nor the severity of bronchiectasis, nor the prevalence of chronic infection with P. aeruginosa. In multivariate regression model, age (OR: 1.05; p-value: <0.0001), low BMI (OR: 2.63; p-value: 0.02), previous hospitalizations (OR: 2.06; p-value: 0.006), and decreasing FEV 1 (OR: 1.02; p-value: 0.001) were independent predictors of 3-year mortality, after adjustment for covariates., Conclusion: Bronchiectasis does not substantially differ across age groups. Poor outcomes in elderly patients with bronchiectasis might be directly related to individual's frailty that should be further investigated in clinical studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Stress urinary incontinence (SUI) is frequently under-reported in patients with chronic lung disease and may have negative psychosocial consequences. We conducted a prospective study to determine the prevalence, severity and treatment outcomes of SUI in female bronchiectasis patients referred for airway clearance techniques. Nineteen out of 40 (48%) patients reported SUI symptoms. Of these, 14 (74%) reported a reduced quality of life secondary to SUI. Following personalised intervention, symptom improvement was observed in 13/19 (68%). Five out of 19 (26%) required specialist referral for further continence care. No associations with lung disease severity and SUI were noted. SUI is common in adult female bronchiectasis patients and should be routinely screened for to improve patients' overall quality of life.

Background and Objective: Hiatal hernias (HH) are associated with gastro-oesophageal reflux and may contribute to lung disease severity. We aimed to evaluate the prevalence of HH among stable non-cystic fibrosis bronchiectasis (NCFB) patients and determine associations with disease severity., Methods: A retrospective cross-sectional cohort study of 100 consecutive NCFB patients in our institution was performed. Data were collected on baseline variables, microbiology, lung function and radiology, according to the modified Bhalla score. Disease severity was assessed using the Bronchiectasis Severity Index (BSI) and FACED severity scores., Results: Following expert radiological review, 81 patients were deemed suitable for study inclusion (mean age (SD) 62.6 (12.4), females 55 (67.9%), body mass index (BMI) 26.9 (5.7)); 29 (35.8%) were HH positive (HH+). HH+ patients had a trend towards higher BMI (P = 0.07), and a significantly higher proportion had reflux symptoms (HH+ 62.1% vs HH- 28.8%, P < 0.01). The presence of HH+ was associated with cystic bronchiectasis (HH+ 30.1%, HH- 11.5%; P = 0.03), increased number of lobes involved (HH+ 2.62 (1.54), HH- 2.17 (1.42); P = 0.03), increased extent of bronchiectasis, (HH+ 6.2 (4.7), HH- 4.5 (3.1); P = 0.04), decreased parenchymal attenuation (HH+ 1.0 (1.8), HH- 0.2 (0.5); P = 0.03) and reduced per cent predicted forced expiratory volume in 1 s (HH+ 75.4% (24.5), HH- 90.4% (25.5); P = 0.02). There was no lobar predilection. HH+ was associated with increased disease severity scores: BSI (HH+ 4.93 (1.65), HH- 3.25 (2.13); P < 0.001) and FACED (HH+ 2.21 (1.52), HH- 1.35 (1.43); P < 0.01)., Conclusions: HH+ was associated with worse disease severity in NCFB patients, characterized by decreased lung function, increased extent and severity of radiological disease, and increased composite disease severity scores., (© 2015 Asian Pacific Society of Respirology.)

Introduction: Idiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study., Methods: In this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared., Results: We found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type., Discussion: Our results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung condition characterised by the accumulation of lipoproteinaceous surfactant material within alveolar airspaces resulting in clinical manifestations ranging from asymptomatic to severe respiratory failure. Three disease subtypes are recognised: autoimmune, secondary and congenital., Methods: We describe two presentations of PAP in the West of Ireland with a review of the current literature., Results: Autoimmune PAP, associated with the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, accounts for >90 % of cases. Treatment with whole lung lavage is the current standard of care. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) and anti-GM-CSF antibodies (rituximab, plasmapharesis) are under investigation., Conclusions: This is a summary of available literature outlining current clinical practice in the diagnosis, management, and treatment of PAP. PAP should be considered in the differential diagnosis of any patient with a restrictive pulmonary defect. Without high clinical suspicion, this diagnosis can easily be missed.

Background: Solitary fibrous tumours of the pleura (SFTPs) are rare pleural mesenchymal neoplasms with distinct clinicopathological and immunohistochemical features, accounting for less than 5 % of all neoplasms involving the pleura., Methods: We present two cases of SFTP with a review of the current literature., Results: Clinical presentation varies according to size and intrathoracic localisation. The molecular pathology of SFTPs is largely unknown. Complete surgical resection is recommended with long-term clinic and radiographic follow-up due to its malignant potential., Conclusions: This is a summary of available literature outlining current clinical practice in the diagnosis, management, and treatment of SFTPs in Ireland.

Bronchiectasis is a chronic debilitating condition with considerable phenotypic diversity. A vicious cycle of infection and inflammation exists in damaged airways with patients suffering from persistent cough, purulent sputum production, recurrent chest infections and general malaise. The associated burden of disease in terms of increased morbidity, reduced quality of life and the socioeconomic cost of long-term management is significant. Further research is essential to improve our understanding of the development and progression of this disease. This article reviews what is currently known about bronchiectasis, its pathophysiology, aetiology and management strategies.

Background: Bronchiectasis is the outcome of a number of different airway insults. Very few studies have characterised the aetiology and utility of a dedicated screening proforma in adult patients attending a general bronchiectasis clinic., Methods: A prospective observational study of 189 bronchiectasis patients attending two centres in the North East of England over a two-year period was performed., Results: The aetiology of bronchiectasis was identified in 107/189(57%) patients. Idiopathic bronchiectasis (IB) represented the largest subgroup (43%). Post-infection bronchiectasis (PIB) constituted the largest proportion (24%) of known causes. Mean age (SD) at diagnosis was 54(20) years with a mean age at symptom onset of 37(24) years, accounting for a diagnostic delay of 17 years. Age of symptom onset was significantly younger in patients with PIB compared to IB (p < 0.0001) and in Pseudomonas sputum positive patients (p = 0.007). Screening for APBA and total immunoglobulin deficiency identified 9 (5%) patients who then had tailored treatment. Routine screening for other aetiologies was deemed unnecessary., Conclusion: IB and PIB accounted for two thirds of cases of bronchiectasis in a general population. We recommend routine screening for ABPA and total immunoglobulin deficiency but not for other rarer aetiologies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: We describe our institutional efficacy experience of azithromycin 250 mg thrice weekly in adult non-cystic fibrosis bronchiectasis., Methods: Eligibility criteria for prophylactic azithromycin included 3 exacerbations requiring rescue antibiotics over the previous 6 months. The clinical records of 56 bronchiectasis patients on azithromycin were retrospectively reviewed. Exacerbation frequency, sputum microbiology, self-reported change in sputum volume, and spirometry results were recorded., Results: Mean length of treatment was 9.1 months (7.5) and 50 patients had treatment > or = 3 months. Spirometry, pre- and post-azithromycin in 29 patients, who had 3 or more months of treatment, showed a mean increase in FEV(1) of 83 ml (0.14) (P=0.005) from 1.560 to 1.643l. There was a decrease in the exacerbation frequency from 0.81/month (SD) (0.32) pre-azithromycin to 0.41/month (0.45) (P<0.001) post-azithromycin. Clinically significant suppression of previous sputum microbial isolates was also observed., Conclusion: Azithromycin improves exacerbation frequency, spirometry, and sputum microbiology in bronchiectasis.

Background and Aim of the Work: Sarcoidosis is a chronic granulomatous disorder of unknown etiology. In most patients the disease is self-limited, although for reasons unclear, others progress or die from progressive organ fibrosis. Growth factors have been implicated in the pathogenesis of other fibrotic lung conditions. We have, therefore, examined the relationship between growth factor expression and disease phenotype in sarcoidosis., Methods: Adopting a target gene approach utilizing gene expression arrays, growth factor gene expression profile was analyzed in the peripheral blood of 12 patients and 12 healthy controls. Expression, functional activity and the effect of oligonucleotide antisense treatment on selected proteins differentially expressed in progressive sarcoidosis were then tested in vitro on primary human lung fibroblasts., Results: Genes regulating angiogenesis were preferentially upregulated in the self-limited form of disease, while early growth response-1 and interleukin-6 were predominantly activated in progressive sarcoidosis. Increased expression of early growth response-1 in sarcoid lung was confirmed by immunohistochemistry. Stimulated human fibroblasts also rapidly expressed interleukin-6 and early growth response-1 and these proteins were found to mediate serum-induced fibroblast proliferation as proliferation could be significantly abrogated with interleukin-6 and early growth response-1 antisense oligonucelotides., Conclusion: We conclude that progressive pulmonary sarcoidosis is characterized by a fibroproliferative dysregulation potentially triggered by early growth response-1 and interleukin-6. Our disease model underlines the inability of steroids to prevent ongoing fibroproliferation in the lung.

Although many lung allograft recipients achieve long-term survival, there is a lack of published data regarding these patients' functional status and quality of life (QoL). We evaluated all 10-year survivors at our institution and, utilizing the SF-36 questionnaire, compared their QoL to population normative and chronic illness data. Twenty-eight (29%) of 96 patients survived > or =10 years following 11 single, 6 bilateral and 11 heart-lung procedures. At the most recent evaluation, median FEV(1) in single and double lung recipients was predicted to be 54% and 74%, respectively. Five (18%) patients had BOS score 0, 13 (46%) BOS 1, 5 (18%) BOS 2 and 5 (18%) BOS 3 and median time to BOS was 7 years. Four (14%) patients required renal replacement therapy. Three patients (11%) developed symptomatic osteoporosis, 2 (7%) post-transplant lymphoma and 1 (4%) an ischaemic stroke. Scores for physical function, role-physical/emotional and general health, but not mental health and bodily pain, were significantly lower compared to normative and chronic illness data. Energy and social-function scores were significantly lower than normative data alone. Long-term survival after lung transplantation is characterized by an absence or delayed development of BOS, low iatrogenic morbidity and preserved mental, but reduced physical health status.

Total lymphoid irradiation (TLI) has been used to control renal and cardiac allograft rejection. Data evaluating TLI in bronchiolitis obliterans syndrome (BOS), the physiological manifestation of chronic lung allograft rejection, is very limited. We present our single center experience of the safety and efficacy of TLI in controlling progressive BOS in a retrospective study. Over 12 years, 37 lung recipients (16 M:21 F) who had undergone 13 single; 12 bilateral and 12 heart-lung transplants were treated with TLI for progressive BOS. Grades at time TLI given were BOS 1 (n = 7) BOS 2 (n = 14) BOS 3 (n = 16). Twenty-seven (73%) completed >8/10 fractions, 10 (27%) failed to complete TLI. Two died from advanced BOS during treatment, 8 stopped early (range 3-7 fractions) due to marrow suppression (6) or infection (2). In the 27 recipients who completed >8/10 fractions, decline in FEV1 was 122.7 mls/month pre-TLI and 25.1 mls/month post-TLI, p = 0.0004, mean (95% CI) change in rate of decline was 97.5 (48.2-146.7) mls/month. TLI significantly reduces the rate of decline in graft function associated with BOS. TLI is well tolerated and associated with few serious complications and is an appropriate immunosuppressive approach in progressive BOS.

Background: HLA-DR2 (15) and 14 (6) have been recently proposed as susceptibility alleles for the development of sarcoidosis and HLA-DR15 as a marker of poor outcome, but validation in other populations is necessary., Methods: Employing serological techniques, we HLA-typed 103 Irish sarcoidosis patients and 105 ethnically-matched healthy controls for class I A and B and II DR and DQ alleles., Results: HLA-B5 (10% vs. 2%, p = 0.018) and DR2 (45% vs. 27%, p = 0.007) were positively associated and B15 (0% vs. 7%, p = 0.01) negatively associated with sarcoidosis compared to control subjects. Seventy-five patients were followed > 2 years and 47 (63%) had chronic and 28 (37%) non-chronic disease. HLA-DR2 (55% vs. 27%, p = 0.001) and DR11 (26% vs. 5%, p<0.0001) were significantly more frequent in chronic disease vs. controls, in contrast to HLA-DR3 (13% vs. 38%, p = 0.002), which had a significant negative association. HLA-B5 (11% vs. 2%, p = 0.029) and DR3 (64% vs. 38%, p = 0.005) were significantly more frequent in non-chronic disease. Of the 29 patients achieving spontaneous remission, 24 (83%) were HLA-DR3 -positive and DR3-positivity was associated with significantly greater carbon monoxide diffusion at follow-up compared to DR3-negative patients (90% vs. 82% predicted, p = 0.027)., Conclusions: This study supports the role of HLA-DR2 (15) as both a susceptibility and poor prognostic marker in sarcoidosis and DR2 positive patients may particularly benefit from close follow-up and early treatment. In contrast, DR3 positive patients are at a much lesser risk of chronic disease. Studies for long-term treatment effects require stratification for HLA-DR2 and DR3 status.

Objective: Susceptibility to sarcoidosis and coeliac disease has been linked to the class II haplotype HLA-DR3, DQ2, and an association between the two disorders has been suggested. As a pilot study, we have sought to determine the prevalence of coeliac disease in a cohort of Irish patients with sarcoidosis., Design: Prospective, case-controlled study., Methods: One hundred and two sarcoid patients (47 males, 55 females) from the west of Ireland and 105 (52 males, 53 females) healthy, ethnically matched, controls underwent interview and screening for coeliac disease and human leucocyte antigen typing by serology. Those with elevated anti-gliadin IgA (AGA) and/or positive endomysial antibody (EMA) were offered small intestinal biopsy., Results: Three (3%) sarcoid patients had a prior diagnosis of coeliac disease. A further 12 (12%) patients and four (4%) controls had elevated AGA (P = 0.047), of whom three and one, respectively, had positive EMA. Small intestinal biopsy in 11 patients and three controls confirmed coeliac disease in one individual each, giving a prevalence of coeliac disease in patients compared with controls of 4/102 (4%) versus 1/105 (1%) (P = 0.21). Sensitivity and specificity of EMA and elevated AGA in sarcoid patients was 100% and 50%, and 50% and 9%, respectively. Of the four affected sarcoid patients, three carried HLA-DR3, DQ2 and one carried DR5 (12), DR7, DQ2., Conclusion: We have demonstrated a moderately increased prevalence of coeliac disease in Irish patients with sarcoidosis, which we feel justifies future screening of our sarcoid population. Estimation of EMA is recommended and should be restricted to those with susceptible haplotypes.

Background: Sarcoidosis is a systemic disorder of unknown cause, highly variable phenotype and unpredictable outcome. Antigen processing, inflammatory response and immunomodulation appear critical to development and prognosis of the disease., Methods: We performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HUG95A, Affymetrix Inc.) for gene expression profiling from peripheral blood of patients with acute pulmonary sarcoidosis (n = 12) and matched healthy controls (n = 12), mean age 36 +/- 12 and 33 +/- 10 years respectively., Results: At follow-up (18 [15-24] months), 7 patients had self-limited disease and 5 had persistent disease. Significantly different expression comparing patients and controls was identified for 1,860 (14.9%) and 729 (5.8%) gene products at p = 0.05 and p = 0.01 levels respectively. Genes closely associated with persistent disease included HLA-DRB1*1501 DQB1*0602, TNFA, NFKB, cyclic AMP-responsive element modulator (CREM) and T-cell activation marker CD69. IL1B, IL8, growth related (GRO)-beta/-gamma and CCR 2,5,6 were closely associated with self-limited disease., Conclusion: We hypothesize that, in self-limited disease, greater effector cell activation leads to successful antigen elimination/tolerance, whereas HLA-DRB1*1501 DQBI*0602-mediated, probably defective/partial T-lymphocyte activation results in an inefficient primary immune response, antigen intolerance and persistent disease.

Background: Chemotherapy is an established intervention in inoperable non-small cell lung cancer (NSCLC), yet few Irish patients receive this treatment., Aim: To determine survival, toxicity and radiological response following chemotherapy for NSCLC at our institution., Methods: Retrospective audit of all patients receiving chemotherapy for histologically proven, inoperable NSCLC from January 1997 to December 2000., Results: There were 80 treatment episodes in 77 patients, mean age 62 years. Forty-eight (60%) patients had locally advanced and 32 (40%) metastatic disease. Mitomycin, Ifosfamide, Carboplatin (MIC) and Paclitaxel/Carboplatin (PC) were the most commonly administered regimens. Median survival for locally advanced and metastatic disease was 13.9 months and 7.1 months respectively. Severe neutropenia and thrombocytopenia were each witnessed after less than 9% of cycles. Eleven (16.7%) patients had radiological response including 4 (6.1%) complete responses., Conclusion: Survival for inoperable NSCLC treated with chemotherapy was encouraging and achieved at low toxicity.