Bronchiectasis in renal transplant patients: a cross-sectional study.

BACKGROUND: Bronchiectasis is a chronic airway disease characterized by permanent and irreversible abnormal dilatation of bronchi. Several studies have reported the development of bronchiectasis after renal transplantation (RT), but no prospective study specifically assessed bronchiectasis in this population. This study aimed to compare features of patients with bronchiectasis associated with RT to those with idiopathic bronchiectasis. METHODS: Nineteen patients with bronchiectasis associated with RT (RT-B group) and 23 patients with idiopathic bronchiectasis (IB group) were prospectively included in this monocentric cross-sectional study. All patients underwent clinical, functional, laboratory, and CT scan assessments. Sputum was collected from 25 patients (n = 11 with RT-B and n = 14 with IB) and airway microbiota was analyzed using an extended microbiological culture. RESULTS: Dyspnea (≥ 2 on mMRC scale), number of exacerbations, pulmonary function tests, total bronchiectasis score, severity and prognosis scores (FACED and E-FACED), and quality of life scores (SGRQ and MOS SF-36) were similar in the RT-B and IB groups. By contrast, chronic cough was less frequent in the RT-B group than in the IB group (68% vs. 96%, p = 0.03). The prevalence and diversity of the airway microbiota in sputum were similar in the two groups. CONCLUSION: Clinical, functional, thoracic CT scan, and microbiological characteristics of bronchiectasis are overall similar in patients with IB and RT-B. These results highlight that in RT patients, chronic respiratory symptoms and/or airway infections should lead to consider the diagnosis of bronchiectasis. Further studies are required to better characterize the pathophysiology of RT-B including airway microbiota, its incidence, and impact on therapeutic management.

Current cough and sputum assessed by the cough and sputum assessment-questionnaire (CASA-Q) is associated with quality of life impairment in cystic fibrosis.

BACKGROUND: Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life. METHODS: This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ). RESULTS: Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis. CONCLUSIONS: CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016).

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

Clinical relevance of low bone density in cystic fibrosis adult patients: A pilot study.

Survival improvement in cystic fibrosis (CF) is associated with more frequent long-term complications, including CF related bone disease (CFBD). Impact of CFBD on global health outcome remains poorly described. We aimed to assess the relationship between low bone mineral density (BMD) and spinal pain, disability, and quality of life in CF adult patients. This monocentric cross-sectional study with prospective data collection was conducted from November 2016 to December 2019 in the Department of Respiratory Diseases at the University Hospital of Reims (NCT02924818). BMD was assessed by X-ray absorptiometry (DXA). Disability was assessed by the Health Assessment Questionnaire (HAQ). Quality of life was assessed by both the St George's Respiratory Questionnaire and the Cystic Fibrosis Questionnaire for teenagers and adults (CFQ 14+). Forty patients were analyzed, 68% of men, with a median age of 25 years, a median body mass index of 21 kg/m² and a median FEV1% of 54%. Nine patients (23%) had spinal pain. Ten patients (25%) had a low BMD. Compared with patients with normal BMD, patients with low BMD had a significantly lower BMI (22 vs 19 kg/m²; P = .006) and less vitamin D supplementation (33% vs 0%; P = .035). Low BMD was not associated with spinal pain, disability and quality of life. Low BMD is frequent in CF, affecting 1-quarter of adult patients. No significant association was found between low BMD and spinal pain, disability or quality of life.

Tracheobronchopathia osteochondroplastica: clinical, bronchoscopic, and comorbid features in a case series.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TO) is a rare condition of unknown etiology. TO is characterized by submucosal nodules, with or without calcifications, protruding in the anterolateral walls of the trachea and proximal bronchi. The objective of this study was to describe TO features and associated comorbidities in a series of patients. METHODS: Patients suffering from TO were retrospectively included by investigators from the Groupe d'Endoscopie Thoracique et Interventionnelle Francophone (GETIF). Demographic, clinical, comorbidities, bronchoscopic, functional, and radiological characteristics, and outcomes were recorded and analyzed. RESULTS: Thirty-six patients were included (69% male with a mean of 65 ± 12 years). Chronic symptoms were described by 81% of patients including cough (74%) and dyspnea on exertion (74%). TO was associated with COPD in 19% of the cases and gastroesophageal reflux disease in 6%. A mild to severe airflow obstruction was present in 55% of the cases. CT scan showed tracheal submucosal nodules in 93% of patients and tracheal stenosis in 17%. Bronchoscopy identified TO lesions in the trachea in 65% of the cases, and 66% of them were scattered. A bronchoscopic reevaluation was performed in 7 cases, 9 ± 14 months [1-56] after initial diagnosis, and showed the stability of lesions in all cases. Three patients underwent interventional bronchoscopic treatment. CONCLUSION: The diagnosis of TO relies on typical bronchoscopic findings and can be evoked on a CT scan. Histologic diagnosis can be useful in atypical cases for differential diagnosis. Given its low consequences in terms of symptoms, lung functions, and evolution, no treatment is usually required.

Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC. METHODS: In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling. FINDINGS: Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported. INTERPRETATION: The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures. FUNDING: French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19.

BACKGROUND: The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. METHODS: Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). RESULTS: Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management. CONCLUSIONS AND CLINICAL IMPLICATION: We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840.

Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors.

BACKGROUND: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. METHODS: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. RESULTS: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. CONCLUSION: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.

Association between obesity-related dyspnea in daily living, lung function and body composition analyzed by DXA: a prospective study of 130 patients.

BACKGROUND: Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We conducted a cross-sectional study to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity. METHODS: One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m2 were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed. RESULTS: Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, p < 0.001), lower lung volumes including Expiratory Reserve Volume (42 ± 28% vs 54 ± 27%, p = 0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, p < 0.001) and Forced expiratory volume in one second (95 ± 13 vs 105 ± 15%, p = 0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m2, p = 0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p = 0.012) and android region (52 ± 4 vs 51 ± 4%, p = 0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea. CONCLUSION: Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated.

Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.

Role of CCR3 in respiratory syncytial virus infection of airway epithelial cells.

Respiratory syncytial virus (RSV) infection is the principal cause of severe lower respiratory tract disease and accounts for a significant risk for developing asthma later in life. Clinical studies have shown an increase in airway responsiveness and a concomitant Th2 response in the lungs of RSV-infected patients. These indications suggest that RSV may modulate aspects of the immune response to promote virus replication. Here, we show that CCR3 facilitates RSV infection of airway epithelial cells, an effect that was inhibited by eotaxin-1/CCL11 or upon CCR3 gene silencing. Mechanistically, cellular entry of RSV is mediated by binding of the viral G protein to CCR3 and selective chemotaxis of Th2 cells and eosinophils. In vivo, mice lacking CCR3 display a significant reduction in RSV infection, airway inflammation, and mucus production. Overall, RSV G protein-CCR3 interaction may participate in pulmonary infection and inflammation by enhancing eosinophils' recruitment and less potent antiviral Th2 cells.

Pulmonary cavitations with increased 18F-FDG uptake revealing a thoracic endometriosis: A case report.

RATIONALE: Thoracic endometriosis is a rare disorder that can involve airways, pleura and lung parenchyma. It is the most frequent form of extra-abdominopelvic endometriosis. Multiple lung cavitations are a rare feature of thoracic endometriosis. PATIENT CONCERNS: A 46-year-old woman was referred to our hospital after incidental finding of multiple pulmonary cavitations with surrounding areas of ground glass opacity on a thoraco-abdominal computed tomography-scan performed for abdominal pain. Retrospectively, the patient also reported mild hemoptysis occurring 4 months ago. DIAGNOSES: Positron emission tomography-computed tomography scan revealed moderate and homogeneous [18F] fluoro-2-deoxy-D-glucose (18F-FDG) uptake in pulmonary cavitations (maximum standardized uptake value 5.7). The diagnosis of thoracic endometriosis was confirmed by histological examination of surgical resection of a left lower lobe cavitation. INTERVENTIONS AND OUTCOME: Gonadotropin-releasing hormone analogues associated with add-back therapy was started. Four months after initiating pharmacological treatment, the chest computed tomography-scan showed a dramatic decrease in lung cavitations size. LESSONS: Thoracic endometriosis is a rare disorder requiring a multidisciplinary management including gynaecologist, pulmonologist, radiologist, nuclear physician, pathologist and thoracic surgeon for early diagnosis and treatment. Our case report highlights that an increased 18F-FDG uptake can be found in thoracic endometriosis syndrome presenting as multiple lung cavitations.

Identifying specific needs in adult cystic fibrosis patients: a pilot study using a custom questionnaire.

BACKGROUND: Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams. METHODS: We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items. RESULTS: Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m2. Mean FEV1% was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school. CONCLUSIONS: Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016.

Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life.

BACKGROUND: While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients. METHODS: Twenty-eight CF patients (18M/10F), with a median age of 27 (22-34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39-93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed. RESULTS: Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8-11) vs 4 (3-6) (p < 0.0001), median depression score of 7 (5-10) vs 1 (1-4) (p < 0.001), with a positive correlation between ISI and HAD anxiety/depression scores (r = 0.702/r = 0.701, respectively, p < 0.0001). Insomnia was also associated with mMRC dyspnea scale ≥ 2, restless legs syndrome, pain and lower SpO2 during sleep. CONCLUSIONS: The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia. TRIAL REGISTRATION: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).

The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. METHODS: CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. RESULTS: Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4+ T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions. CONCLUSIONS: The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

Prevalence and Impact of Rheumatologic Pain in Cystic Fibrosis Adult Patients.

BACKGROUND: With the improvement of cystic fibrosis (CF) patient survival, the prevalence of long-term complications increased, among them rheumatologic disorders. METHODS: The aim of this prospective study was to evaluate the prevalence of spinal and joint pain, and their impact on disability, anxiety, depression, and quality of life in CF adult patients. RESULTS: Forty-seven patients were analyzed, 72% of men, mean aged 28 years, with a mean body mass index of 22 kg/m2 and a mean FEV1% of 63%. Twenty-two patients (47%) described rheumatologic pain either spinal (n = 15, 32%) and/or joint pain (n = 14, 30%). Patients with spinal and/or joint pain were shorter (p = 0.023), more frequently colonized with Staphylococcus aureus (p < 0.008), had more frequent ΔF508 homozygous mutations (p = 0.014), and a trend for more impairment of the 6-min walking distance (p = 0.050). The presence of rheumatologic pain tended to be associated with disability according to the Health Assessment Questionnaire (HAQ) and anxiety. Compared with patients with no pain patients with both spinal and joint pain exhibited a more pronounced impact on the St George's Respiratory Questionnaire (SGRQ). CONCLUSION: Rheumatologic pain is frequent in CF adult patients, and may affect daily living, anxiety and quality of life. Systematic assessment of rheumatologic pain should be included in the management of CF patients.

Acute severe idiopathic lymphoid interstitial pneumonia: A case report.

RATIONALE: Lymphoid interstitial pneumonia is a rare benign pulmonary lymphoproliferative disorder usually presenting with a sub-acute or chronic condition and frequently associated with autoimmune disorders, dysgammaglobulinemia, or infections. PATIENT CONCERNS: A 74-year-old woman with no past medical history presented with acute dyspnea, nonproductive cough, hypoxemia (room air PaO2: 48 mmHg) and bilateral alveolar infiltrates with pleural effusion. Antibiotics and diuretics treatments did not induce any improvement. No underlying condition including cardiac insufficiency, autoimmune diseases, immunodeficiency, or infections was found after an extensive evaluation. Bronchoalveolar lavage revealed a lymphocytosis (60%) with negative microbiological findings. High-dose intravenous corticosteroids induced a mild clinical improvement only, which led to perform a surgical lung biopsy revealing a lymphoid interstitial pneumonia with no sign of lymphoma or malignancies. DIAGNOSES: Acute severe idiopathic lymphoid interstitial pneumonia. INTERVENTIONS: Ten days after the surgical lung biopsy, the patient experienced a dramatic worsening leading to invasive mechanical ventilation. Antibiotics and a new course of high-dose intravenous corticosteroids did not induce any improvement, leading to the use of rituximab which was associated with a dramatic clinical and radiological improvement allowing weaning from mechanical ventilation after 10 days. OUTCOMES: Despite the initial response to rituximab, the patient exhibited poor general state and subsequent progressive worsening of respiratory symptoms leading to consider symptomatic palliative treatments. The patient died 4 months after the diagnosis of lymphoid interstitial pneumonia. LESSONS: Idiopathic lymphoid interstitial pneumonia may present as an acute severe respiratory insufficiency with a potential transient response to rituximab.

Assessment of TNF-α inhibitors in airway involvement of relapsing polychondritis: A systematic review.

Relapsing polychondritis (RP) is a rare immune-mediated disease affecting cartilaginous structures. Respiratory tract manifestations are frequent and constitute a major cause of morbidity and mortality. The present review of the literature was designed to assess the efficacy of tumor necrosis factor alpha (TNF-α) inhibitors in respiratory tract involvement of RP.A MEDLINE literature search was performed from January 2000 to December 2016 to identify all studies and case reports of anti-TNF-α therapy in RP. Articles published in English or French concerning patients with respiratory tract involvement were eligible. Two authors (JB, FL) independently reviewed and extracted data concerning each patient and 2 personal cases were added. Treatment efficacy was assessed according to systemic and/or respiratory criteria.A total of 28 patients (mean age: 41.6 years; 16 females/12 males) were included in the final analysis. Anti-TNF-α therapy was associated with improved health status and respiratory symptoms in 67.8% and 60.1% of cases, respectively.These results suggest that TNF-α inhibitors could be considered for the treatment of respiratory tract involvement of RP.

Pulmonary adverse events related to idelalisib therapy: A single centre experience.

Idelalisib is a potent and selective inhibitor of the PI3Kδ approved since September 2014 for the treatment of several types of B cell malignancies. Pulmonary adverse events related to idelalisib are an emerging serious adverse event. We report here a single centre cohort of 16 patients who initiated idelalisib as routine treatment. Five of them experienced severe pulmonary adverse events related to idelalisib therapy. Comparison of the 5 patients with severe pulmonary events versus the 11 patients without identified no predisposing factors. Severe pulmonary adverse events were related to infectious pneumonia and/or to a drug-induced pneumonitis. The mechanisms of idelalisib-associated pneumonitis are unknown but consistent with the drug-induced pneumonitis described with mTOR inhibitors. Indeed, by inhibiting PI3Kδ, idelalisib also inhibits the mTOR pathway. Clinicians should be aware that any idelalisib-treated patient who presents with pulmonary symptoms should be evaluated for pneumonitis. Corticosteroids should be considered in addition to anti-infective therapy in case of severe pneumonitis or persistent pulmonary symptoms despite adequate antibiotic therapy.

Hereditary multiple exostoses of the ribs as an uncommon cause of pneumothorax: A case report.

RATIONALE: Hereditary multiple exostoses (HME) is a genetic musculoskeletal condition causing multiple exostoses. Rib location of exostosis can be complicated by thoracic injuries. PATIENT CONCERNS AND DIAGNOSES: We report a case of pneumothorax in a 32-year-old man with a partial left-sided pneumothorax caused by an exostosis of the fourth and fifth ribs. INTERVENTIONS AND OUTCOMES: Clinical and radiological presentations allowed a conservative management. A video-assisted thoracoscopic surgery was performed a few weeks later to avoid any recurrence. LESSONS: Rib exostosis represents an unusual cause of pneumothorax. Any local modification of symptoms or size of the exostosis should lead to investigations in regard to chondrosarcoma transformation.