Airway 'Resistotypes' and Clinical Outcomes in Bronchiectasis.

INTRODUCTION: Application of whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis highlights a diverse pool of antimicrobial resistance genes: the 'resistome', the clinical significance of which remains unclear. METHODS: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n=280) including the international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 study (CAMEB 2; n=251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing P. aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing and the bronchiectasis resistome evaluated in association with clinical outcomes and underlying host microbiomes. RESULTS: The bronchiectasis resistome features a unique resistance gene profile and elevated counts of aminoglycoside, bicyclomycin, phenicol, triclosan and multi-drug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles including increased macrolide and multi-drug resistance genes associate with shorter intervals to next exacerbation, while distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant 'resistotypes' RT1 and RT2, the latter characterized by poor clinical outcomes, increased multi-drug resistance and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favourable resistome profile demonstrating reduced resistance gene diversity. CONCLUSION: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis 'resistotypes' link to clinical disease and are modifiable through targeted antimicrobial therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD.

BACKGROUND: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown. METHODS: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes. RESULTS: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus-sensitised COPD of patients with frequent exacerbations. CONCLUSION: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens.

Predictors of Influenza PCR Positivity in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

PURPOSE: Influenza infection is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Clinical features predicting influenza PCR positivity are unknown. We aim to identify predictors of influenza PCR positivity in AECOPD. PATIENTS AND METHODS: A retrospective study of AECOPD cases admitted between 1st January 2016 to 30 June 2017 with combined nasal/throat swabs sent for influenza PCR (Xpert Xpress Flu/RSV) within 24 hours of admission was performed. Clinical parameters and investigations within 24 hours of admission were retrieved from electronic medical records. RESULTS: Influenza PCR were sent for 925 AECOPD cases (mean age 75 years, 87.9% male). There were 90 PCR positive cases (68 Influenza A, 22 Influenza B). Influenza PCR positive cases had higher temperatures, higher heart rates, lower white cell and lower eosinophil counts. Age, gender, COPD severity, comorbidities and smoking status were similar in both groups. There were no differences in blood pressure, oxygen status, neutrophil or lymphocyte counts, C reactive protein, procalcitonin or chest X-ray consolidation between groups. Higher temperature, higher heart rate, white cell count in the lowest quartile (Q1 < 8.1 x109/L) and non-eosinophilic exacerbations predicted influenza PCR positivity on univariate logistic regression and these factors remained significant after multivariate adjustment (temperature adjusted odds ratio [adj OR] 1.324 [1.009-1.737], p = 0.043; heart rate adj OR 1.017 [1.004-1.030], p = 0.011; white cell count Q1 adj OR 3.330 [1.690-6.562], p = 0.001; eosinophilic exacerbations adj OR 0.390 [0.202-0.756], p = 0.005). CONCLUSION: Higher temperature, higher heart rate, low white cell count (especially when < 8.1 x109/L) and non-eosinophilic exacerbations are independent predictors of influenza PCR positivity in AECOPD cases.

High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? STUDY DESIGN: Prospective, observational, cross-sectional study. METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.

Epidemiology and economic burden of bronchiectasis requiring hospitalisation in Singapore.

BACKGROUND AND OBJECTIVE: Little is known about the epidemiology and cost of bronchiectasis in Asia. This study describes the disease burden of bronchiectasis in Singapore. METHODS: A nationwide administrative dataset was used to identify hospitalisations with bronchiectasis as a diagnosis. Population statistics and medical encounter data were used to estimate the incidence, mortality, prevalence and direct medical costs associated with bronchiectasis requiring hospitalisation. RESULTS: There were 420 incident hospitalised bronchiectasis patients in 2017, giving an incidence rate of 10.6 per 100 000. Age-standardised incidence declined on average by 2.7% per year between 2007 and 2017. Incidence rates increased strongly with age in both men and women. Tuberculosis was a secondary diagnosis in 37.5% of incident hospitalisations in 2007, but has declined sharply since then. Patient survival was considerably lower in both men (5-year relative survival ratios (RSR) 0.63, 95% CI 0.59-0.66) and women (5-year RSR 0.75, 95% CI 0.72-0.78). The point prevalence of bronchiectasis was 147.1 per 100 000 in 2017, and increased sharply with age, with >1% of people aged ≥75 years having bronchiectasis. Total first-year costs among incident bronchiectasis patients in 2016 varied widely, with a mean±sd USD 7331±8863. Approximately 10% of the patients admitted in 2016 had total first-year costs of more than USD 14 380. CONCLUSION: Bronchiectasis is common and imposes a substantial burden on healthcare costs and survival rates of patients in Singapore.

Integrative microbiomics in bronchiectasis exacerbations.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.

Conventional vs high-sensitive troponins in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Cardiac troponins (cTn), either conventional or high-sensitive (hscTn) assays, are often performed during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). OBJECTIVES: To compare factors affecting abnormal conventional cTn and hscTn. METHODS: We retrospectively studied data from AECOPD patients with conventional or hscTn performed at presentation. Binary logistic regression was used to identify predictors for abnormal conventional cTn (>0.5 ug/L) and hscTn (>40 ng/L). RESULTS: There were 466 patients in the conventional cTn and 313 patients in the hscTn groups. Ischaemic electrocardiographic change was the only significant predictor for abnormal conventional cTn (OR 6.662 [CI 1.233-35.990], p = 0.028) while B-type natriuretic peptide levels (Adj OR 1.004 [CI 1.000-1.006], p = 0.010) and SpO2/FiO2 ratio (Adj OR 0.115 [CI 0.017-0.069], p = 0.026) were significant predictors of abnormal hscTn. CONCLUSIONS: Predictors of abnormal cTn differ between assays and should be taken into consideration when interpreting cTn during AECOPD.

A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain. METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi. RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality. CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.

Reversible platypnea-orthodeoxia in COVID-19 acute respiratory distress syndrome survivors.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical syndrome characterized by orthostatic oxygen desaturation and positional dyspnea from supine to an upright position. We observed POS in 5 of 20 cases of severe 2019 novel coronavirus (COVID-19) pneumonia, which demonstrated persistently elevated shunt fraction even after liberation from mechanical ventilation. POS was first observed during physiotherapy sessions; median oxygen desaturation was 8 % (range: 8-12 %). Affected individuals were older (median 64 vs 53 years old, p = 0.05) and had lower body mass index (median 24.7 vs 27.6 kg/m2, p = 0.03) compared to those without POS. While POS caused alarm and reduced tolerance to therapy, this phenomenon resolved over a median of 17 days with improvement of parenchymal disease. The mechanisms of POS are likely due to gravitational redistribution of pulmonary blood flow resulting in increased basal physiological shunting and upper zone dead space ventilation due to the predominantly basal distribution of consolidative change and reported vasculoplegia and microthrombi in severe COVID-19 disease.

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

INTRODUCTION: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear. METHODS: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome. RESULTS: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD. CONCLUSION: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD.

Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis.

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.

"High-Risk" Clinical and Inflammatory Clusters in COPD of Chinese Descent.

BACKGROUND: COPD is a heterogeneous disease demonstrating inter-individual variation. A high COPD prevalence in Chinese populations is described, but little is known about disease clusters and prognostic outcomes in the Chinese population across Southeast Asia. We aim to determine if clusters of Chinese patients with COPD exist and their association with systemic inflammation and clinical outcomes. RESEARCH QUESTION: We aim to determine if clusters of Chinese patients with COPD exist and their association with clinical outcomes and inflammation. STUDY DESIGN AND METHODS: Chinese patients with stable COPD were prospectively recruited into two cohorts (derivation and validation) from six hospitals across three Southeast Asian countries (Singapore, Malaysia, and Hong Kong; n = 1,480). Each patient was followed more than 2 years. Clinical data (including co-morbidities) were employed in unsupervised hierarchical clustering (followed by validation) to determine the existence of patient clusters and their prognostic outcome. Accompanying systemic cytokine assessments were performed in a subset (n = 336) of patients with COPD to determine if inflammatory patterns and associated networks characterized the derived clusters. RESULTS: Five patient clusters were identified including: (1) ex-TB, (2) diabetic, (3) low comorbidity: low-risk, (4) low comorbidity: high-risk, and (5) cardiovascular. The cardiovascular and ex-TB clusters demonstrate highest mortality (independent of Global Initiative for Chronic Obstructive Lung Disease assessment) and illustrate diverse cytokine patterns with complex inflammatory networks. INTERPRETATION: We describe clusters of Chinese patients with COPD, two of which represent high-risk clusters. The cardiovascular and ex-TB patient clusters exhibit high mortality, significant inflammation, and complex cytokine networks. Clinical and inflammatory risk stratification of Chinese patients with COPD should be considered for targeted intervention to improve disease outcomes.

Impact of an interstitial lung disease service in the diagnosis and management of interstitial lung disease in Singapore.

INTRODUCTION: The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore. METHODS: A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017. RESULTS: Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service. CONCLUSION: The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

Epidemiological and pathophysiological evidence supporting links between obstructive sleep apnoea and Type 2 diabetes mellitus.

Obstructive sleep apnoea (OSA) and Type 2 diabetes mellitus (T2DM) are common diseases. The global prevalence of OSA is between 2% and 7% in general population cohorts. The worldwide prevalence of T2DM among adults (aged 20-79 years) was estimated to be 6.4%. The concurrent presence of OSA and T2DM can be expected in the same patient, given their high prevalence and similar predisposition. We reviewed the overlapping pathophysiology of OSA and T2DM in this article.

Distinct "Immunoallertypes" of Disease and High Frequencies of Sensitization in Non-Cystic Fibrosis Bronchiectasis.

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 immune-inflammatory 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.

Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study.

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 ClavisporaAspergillus 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.

Reversible platypnoea-orthodeoxia syndrome in post-tuberculosis bronchial stenosis.

Bronchial stenosis is known to complicate endobronchial tuberculosis despite medical therapy. It is often associated with dyspnoea. In severe cases, bronchial stenosis results in airflow obstruction, impaired secretion clearance, and can lead to respiratory failure. We present an unusual observation of platypnoea-orthodeoxia syndrome in a young woman with acute atelectasis due to post-tuberculosis bronchial stricture. Imaging revealed complete middle and right lower lobe atelectasis with a partially aerated right upper lobe. In the sitting posture, there was positional worsening of dyspnoea associated with an increase in the alveolar-arterial oxygen gradient and shunt fraction. The likely mechanism was due to gravitational difference in ventilation-perfusion matching. The platypnoea-orthodeoxia syndrome was reversible following balloon dilatation of the bronchial stenosis and expansion of the collapsed lung.