BackgroundThe role of bronchoalveolar lavage fluid (BAL) lymphocyte% to diagnose chronic hypersensitivity pneumonitis (CHP) is unclear. We conducted a systematic review and meta-analysis of BAL lymphocyte% in the diagnosis of CHP.MethodsWe searched Medline, Embase and Cochrane library from inception to August 2019. Individual patient data were obtained to test performance characteristics of BAL lymphocyte% at different thresholds. Random-effects models were used for pooled estimates, with comparisons made between CHP and non-CHP interstitial lung diseases (ILD).ResultsFifty-three studies were included in the systematic review and 42 in the meta-analysis. The pooled estimate for BAL lymphocyte% was 42.8% (95%CI 37.7–47.8, I2=95.3%) in CHP, 10.0% (95%CI 6.9–13.1, I2=91.2%) in idiopathic pulmonary fibrosis (IPF), 23.1% (95% CI 3.0–43.2, I2=85.2%) in non-IPF idiopathic interstitial pneumonia (IIP), 23.4% (95%CI 11.0–35.9, I2=45.7%) in connective-tissue disease ILD (CTD-ILD), and 31.2% (95% CI 17.6–44.8, I2=95.2%) in sarcoidosis. Results differed between CHP and IPF (p<0.0001), non-IPF IIP (p=0.0309), and CTD-ILD (p=0.0824), but not between sarcoidosis (p=0.0966). Using individual patient data from eight studies, lymphocyte% threshold >20% provided sensitivity of 68.1% and specificity of 64.8% for CHP. Higher thresholds provided lower sensitivity with higher specificity. Older age and ever having smoked were associated with lower lymphocyte% in CHP.ConclusionsBAL lymphocyte% is higher in CHP compared to IPF and other IIP, with higher thresholds providing improved specificity at the cost of sensitivity. However, parent studies are at risk of incorporation bias, and prospective studies should evaluate the additive discriminate value of BAL lymphocyte% to accurately diagnose CHP.

IntroductionInterstitial lung disease (ILD) is a frequent manifestation of connective tissue disease (CTD) with substantial variability in prevalence and outcomes reported across CTD subtypes. This systematic review summarises the prevalence, risk factors and ILD patterns on chest computed tomography of CTD-ILD.MethodsA comprehensive search was performed in Medline and Embase to identify eligible studies. Meta-analyses were completed using a random effects model to determine the pooled prevalence of CTD-ILD and ILD patterns.Results11 582 unique citations were identified with 237 articles included. Pooled prevalence of ILD was 11% in rheumatoid arthritis (95% CI 7–15%), 47% in systemic sclerosis (44–50%), 41% in idiopathic inflammatory myositis (33–50%), 17% in primary Sjögren's syndrome (12–21%), 56% in mixed connective tissue disease (39–72%) and 6% in systemic lupus erythematosus (3–10%). Usual interstitial pneumonia was the most prevalent ILD pattern in rheumatoid arthritis (pooled prevalence of 46%), while nonspecific interstitial pneumonia was the most common ILD pattern in all other CTD subtypes (pooled prevalence range 27–76%). Across all CTDs with available data, positive serology and higher inflammatory markers were risk factors for development of ILD.DiscussionWe identified substantial variability in ILD across CTD subtypes suggesting that CTD-ILD is too heterogenous to be considered a single entity.

As the SARS-CoV-2 virus (COVID-19) continues to affect people across the globe, there is limited understanding of the long term implications for infected patients. While some of these patients have documented follow-ups on clinical records, or participate in longitudinal surveys, these datasets are usually designed by clinicians, and not granular enough to understand the natural history or patient experiences of "long COVID". In order to get a complete picture, there is a need to use patient generated data to track the long-term impact of COVID-19 on recovered patients in real time. There is a growing need to meticulously characterize these patients' experiences, from infection to months post-infection, and with highly granular patient generated data rather than clinician narratives. In this work, we present a longitudinal characterization of post-COVID-19 symptoms using social media data from Twitter. Using a combination of machine learning, natural language processing techniques, and clinician reviews, we mined 296,154 tweets to characterize the post-acute infection course of the disease, creating detailed timelines of symptoms and conditions, and analyzing their symptomatology during a period of over 150 days.

We thank O. Moran-Mendoza and M. Khalil for their interest in our work. In their correspondence, they highlight differences between our findings and others, suggesting a re-analysis of our data after excluding studies that used bronchoalveolar lavage (BAL) lymphocyte % as part of the diagnostic criteria for fibrotic hypersensitivity pneumonitis (HP), in an effort to reduce incorporation bias. Given the absence of studies meeting these criteria, we find this suggestion unfeasible.As outlined in both our manuscript [1] and the recent American Thoracic Society/Japanese Respiratory Society/Asociación Latinoamericana del Tórax guidelines for HP [2], there are no randomised controlled trials or controlled observational studies evaluating BAL lymphocyte % as a diagnostic test for fibrotic HP. Both systematic reviews and meta-analyses included only observational studies reporting on BAL lymphocyte % in patients with fibrotic HP [3]. A subset of the 42 studies included in our meta-analysis explicitly stated inclusion of BAL lymphocyte % in the diagnostic criteria for HP (n=22), 10 studies did not state inclusion of BAL in diagnostic criteria, and 10 studies reported unclear case definitions. However, given that BAL lymphocyte % were reported in each parent study, it is prudent to assume that BAL was undertaken for clinical purposes and informed the HP diagnoses; otherwise it would not have been performed or reported. Erroneously assuming that BAL lymphocyte % was not incorporated into the diagnostic evaluation in these circumstances would introduce serious bias. Notably, the HP guideline committee performed a sensitivity analysis removing studies that explicitly stated incorporation of BAL lymphocyte % as part of their diagnostic criteria for HP [3]. Results were unchanged, so those papers were ultimately kept in their final analysis. In their discussion, they comment that inclusion bias cannot be excluded because BAL findings may have influenced the final diagnosis of HP, even if it was not described. That two large robustly conducted systematic reviews did not identify a single study that definitively addressed the research question of interest should confirm that no such studies currently exist to inform the additive discriminative value of BAL lymphocyte % in the diagnosis of fibrotic HP.

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