Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.
Persistent air-leak in patients with spontaneous pneumothorax (SP) is not uncommon and may present a management dilemma in those who are unfit or unwilling for surgery. Video-assisted thoracoscopic surgery (VATS) has been advocated in the management of patients with broncho-pleural fistulae (air-leak persisting beyond 7 days): however the optimum time for surgical intervention remains unclear. We reviewed the records of 130 episodes of SP in 115 patients over a 2-year period to determine clinical course and outcome, particularly with respect to duration of air-leak. There were 90 first episodes and 40 recurrent episodes. Eighty-one episodes (62%) occurred in patients with underlying lung disease (secondary pneumothorax). Initial management consisted of chest-tube drainage in 104 episodes (80%) occurring in 90 patients, percutaneous needle aspiration in five patients (4%) and observation in 21 episodes (16%) in 20 patients. In the group treated with chest-tube drainage, there was spontaneous resolution of air leak and lung re-expansion in 90 episodes (87%). The overall incidence of broncho-pleural fistula was 34.6%. In the primary SP group. 75% of air-leaks ceased by 7 days and 100% by 15 days. In the secondary SP group, 61% of air-leaks resolved by 7 days and 79% by 14 days, after which time resolution of air-leak proceeded at a much slower rate. Five patients underwent surgery while nine patients were discharged with residual pneumothoraces. There were no major complications or mortality. Based on our findings, we advocate surgery for patients with air-leak persisting beyond 14 days, while favouring a conservative approach before this time, as the majority of air-leaks (especially in patients with primary pneumothorax) would resolve by 14 days.
AimWe studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion.MethodsRetrospective analysis of patients hospitalized with exudative pleural effusion in 2013.ResultsSerum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45–0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0–1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99–1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92–0.99) and 0.94 (95 % CI 0.83–0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7–99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01–0.15).ConclusionHigher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.
Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear.Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immuneinflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined. Measurements and Main Results:A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.
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