Heterozygous TERT gene mutation associated with familial idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown cause that occurs sporadically, but it can also occur in families and so named as Familial Pulmonary Fibrosis (FPF). Some forms of FPF overlaps IPF features, namely the radiological and histological pattern of usual interstitial pneumonia (UIP). Genetic and environmental factors commonly play an important role in the pathogenesis of FPF and the most commonly identified mutations involve the telomerase complex. Here, we report a rare case of FPF in a male at the age of 44, in whom genetic testing showed heterozygous variants for the telomerase reverse transcriptase gene (TERT). Our report highlights the importance of compiling a thorough family history in younger patients identified with UIP serving as a resource for identifying the current and future genetic links to disease. Families with UIP hold a great promise in defining UIP pathogenesis, potentially suggesting targets for the development of future therapies.

Organizing pneumonia revisited: insights and uncertainties from a series of 67 patients.

Background: Organizing pneumonia (OP) is classified as an acute/subacute pneumonia according to the American Thoracic Society/European Respiratory Society statement (2013 update). Although its clinical presentation, radiologic and histologic features are well established, data on the relevance of potential causes, corticosteroid doses and length, or management of relapses are based on heterogeneous series of patients. Objectives: The aims of this study were to describe clinical presentation, diagnosis and treatment of OP, explore potential causes, discuss strategies for managing relapses, and analyze prognostic factors. We also discuss our findings in relation to relevant data in the literature. Methods: We performed a cross-sectional study of all patients diagnosed with OP at a tertiary referral center in northern Portugal between 2008 and 2015. Results: Sixty-seven patients were diagnosed with OP over the 7-year study period. Dyspnea and cough were the most common presenting symptoms and approximately 30% of patients were hospitalized at the time of diagnosis. Approximately half of the patients were receiving drugs described as potential causes of OP. Microorganisms were isolated in approximately one-third of patients. Other potential causes identified were hematologic disorders, neoplasms, connective tissue diseases, myelodysplastic syndromes, immunodeficiencies, radiotherapy, and bird exposure. Cryptogenic OP was diagnosed in just 16 patients (23.8%). Corticosteroids were the most common treatment and 11 patients (16.4%) experienced relapse. Conclusions: The findings for this series of patients confirm the extreme variability of the contexts in which OP can occur and suggest that rather than a distinct, homogeneous clinicopathologic entity, OP is a non-specific reaction whose outcomes are dependent on the cause. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 129-138).

Idiopathic pulmonary fibrosis--clinical presentation, outcome and baseline prognostic factors in a Portuguese cohort.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is the most common disease in the subgroup of idiopathic interstitial pneumonias. It is inevitably associated to a bad prognosis, although assuming a highly variable clinical course. METHODS: Patients with IPF, observed at Interstitial Lung Diseases outpatient clinic of Centro Hospitalar de São João - Porto, Portugal, were identified and clinical, functional, radiological and bronchoalveolar lavage (BAL) parameters were reviewed. Their clinical course and survival were analyzed in order to identify prognostic factors. RESULTS: Eighty-one patients were included, with a mean age at diagnosis of 63.8 years old. At diagnosis, the main functional abnormalities were restrictive physiology, reduced lung diffusion and exercise capacity impairment. Clinical course was mainly slowly progressive (72.3%). Ten patients (13.2%) had a rapid progression and 11 (14.5%) patients had an acute exacerbation during the course of the disease. IPF's rapid progression was associated to a higher functional impairment at diagnosis, namely in what is related with Forced Vital Capacity (FVC) and Total Lung Capacity (TLC). Median survival was 36 months. A significant difference in survival was observed among different types of clinical course - 41 months for slow progressors and 9 months for rapid progressors. Lower levels of FVC, TLC, 6th minute walk test distance and rest PaO2, and higher BAL neutrophil count were associated with poorer survival in univariate analysis. CONCLUSION: The analysis of this group of IPF patients confirms two clearly different phenotypes, slow and rapid progressors. Those phenotypes seem to have different presentations and a remarkably different natural history. These results could mean different physiopathologic pathways, which could implicate different therapeutic approaches.

Predictors of delayed sputum smear and culture conversion among a Portuguese population with pulmonary tuberculosis.

INTRODUCTION: Failure of sputum smear and/or culture conversion after 2 months of tuberculosis (TB) treatment has been considered a predictor of patient infectivity and treatment failure. We aimed to identify the factors associated with delayed sputum smear and culture conversion in patients with pulmonary TB who were given anti-TB treatment. MATERIAL AND METHODS: Retrospective cohort of 136 adult patients with sputum culture-proven pulmonary TB referred to an urban Chest Disease Centre. Socio-demographic, clinical, radiological, microbiological, and therapeutic data were evaluated. RESULTS: The median age was 41.0 (interquartile range [IQR] 18.0) years and 75.0% of patients were male. Delayed sputum smear and culture conversion occurred in 25.4% (30/118) and 27.2% (37/136) of patients, respectively. Multivariate analysis indicated that age ≥ 50 years (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.5-13.3), male gender (OR 10.8, 95% CI 1.3-91.1), and smear grade > 1-9 acid fast bacilli (AFB)/field (3+) (OR 11.7, 95% CI 1.4-100.6) were significantly associated with persistent smear positivity after 2 months of treatment. Bilateral radiological involvement (OR 3.7, 95% CI 1.5-9.0) and colony count > 100 (3+) (OR 5.8, 95% CI 1.2-27.4) were significantly associated with persistent culture positivity. CONCLUSIONS: Delayed sputum smear and culture conversion occurred in about one third of patients. Older age, male gender, and higher bacillary load were independently associated with delayed smear conversion. Bilateral radiological involvement and higher colony count were independently associated with delayed culture conversion.

Prevalence of new-onset insomnia in patients with obstructive sleep apnoea syndrome treated with nocturnal ventilatory support.

INTRODUCTION: New-onset insomnia (NOI) associated with nocturnal ventilatory support (NVS) is becoming a reality in clinical practice; however there is a lack of data about its prevalence. Our aim was to determine the prevalence of NOI in patients with obstructive sleep apnoea syndrome (OSAS) under NVS and its associated risk factors. MATERIAL AND METHODS: Descriptive cross-sectional study of 80 patients with OSAS under NVS. We compared two groups, with and without NOI, considering demographic characteristics, disease features, and personality. Patients under anxiolytic and/or antidepressant medication, with a weight loss of 10% or greater, and with restless legs symptoms were excluded. RESULTS: Median age of patients was 60.0 (interquartile range (IQR) 10.0) years; 82.5% were male. Median initial Epworth Sleepiness Scale (ESS) and apnoea-hypopnoea index (AHI) were 12.5 (IQR 9.0) and 44.1 (IQR 22.4)/hr, respectively. The majority of patients (91.3%) were under auto-adjusting positive airway pressure (APAP). Insomnia at baseline was present in 30% of patients (n=24). Prevalence of NOI was 21.4% (12/56). Initial and/or intermediate insomnia were the most frequent subtypes (n=11). We found a statistically significant negative relation between NOI and pressure on 90% night-time (P(90)) (p=0.040). CONCLUSIONS: OSAS patients under NVS presented a high prevalence of NOI. Patients with NOI presented lower levels of pressure using NVS, compared to the others.

[Azithromycin as an adjuvant therapy in cryptogenic organizing pneumonia]. / Azitromicina como terapêutica adjuvante na pneumonia organizativa criptogénica.

There are literature data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP) as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy. A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500mg, on alternate days) as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week) with no documentation of adverse side effects. This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy.