Prevalence and assessment of frailty in interstitial lung disease - a systematic review and meta-analysis.

BACKGROUND Frailty is a multisystem dysregulation that challenges homeostasis and increases vulnerability towards stressors. In patients with interstitial lung diseases (ILD) frailty is associated with poorer lung function, greater physical impairment, and higher symptom burden. Our understanding of the prevalence of frailty in ILD and consequently its impact on the ILD population is limited. OBJECTIVE AND METHODS We aimed to systematically review frailty assessment tools and to determine frailty prevalence across different ILD cohorts. Meta-analyses were used to calculate the pooled prevalence of frailty in the ILD population. RESULTS We identified 26 studies (15 full-texts, 11 conference abstracts) including a total of 4614 patients with ILD. The most commonly used frailty assessment tools were the Fried Frailty Phenotype (FFP), the Short Physical Performance Battery (SPPB), and the cumulative Frailty Index (FI). Data allowed for meta-analyses of FFP and SPPB prevalence. The pooled prevalence of frailty was 35% (95% CI 25%-45%) by FFP, and 19% (95% CI 12%-28%) by SPPB. CONCLUSIONS Frailty is common in ILD, with considerable variability of frailty prevalence depending on the frailty assessment tool used. These findings highlight the importance of frailty in ILD and the need for a standardized approach to frailty assessment in this population

Social Media Content of Idiopathic Pulmonary Fibrosis Groups and Pages on Facebook: Cross-sectional Analysis.

BACKGROUND Patients use Facebook as a resource for medical information. We analyzed posts on idiopathic pulmonary fibrosis (IPF)-related Facebook groups and pages for the presence of guideline content, user engagement, and usefulness. OBJECTIVE The objective of this study was to describe and analyze posts from Facebook groups and pages that primarily focus on IPF-related content. METHODS Cross-sectional analysis was performed on a single date, identifying Facebook groups and pages resulting from separately searching "IPF" and "idiopathic pulmonary fibrosis." For inclusion, groups and pages needed to meet either search term and be in English, publicly available, and relevant to IPF. Every 10th post was assessed for general characteristics, source, focus, and user engagement metrics. Posts were analyzed for presence of IPF guideline content, useful scientific information (eg, scientific publications), useful support information (eg, information about support groups), and potentially harmful information. RESULTS Eligibility criteria were met by 12 groups and 27 pages, leading to analysis of 523 posts. Of these, 42% contained guideline content, 24% provided useful support, 20% provided useful scientific information, and 5% contained potentially harmful information. The most common post source was nonmedical users (85%). Posts most frequently focused on IPF-related news (29%). Posts containing any guideline content had fewer likes or comments and a higher likelihood of containing potentially harmful content. Posts containing useful supportive information had more likes, shares, and comments. CONCLUSIONS Facebook contains useful information about IPF, but posts with misinformation and less guideline content have higher user engagement, making them more visible. Identifying ways to help patients with IPF discriminate between useful and harmful information on Facebook and other social media platforms is an important task for health care professionals

The Octopus Sign-A New HRCT Sign in Pulmonary Langerhans Cell Histiocytosis.

Background: Fibrosis in pulmonary Langerhans cell histiocytosis (PLCH) histologically comprises a central scar with septal strands and associated airspace enlargement that produce an octopus-like appearance. The purpose of this study was to identify the octopus sign on high-resolution computed tomography (HRCT) images to determine its frequency and distribution across stages of the disease. Methods: Fifty-seven patients with confirmed PLCH were included. Two experienced chest radiologists assessed disease stages as early, intermediate, or late, as well as the lung parenchyma for nodular, cystic, or fibrotic changes and for the presence of the octopus sign. Statistical analysis included Cohen's kappa for interrater agreement and Fisher's exact test for the frequency of the octopus sign. Results: Interobserver agreement was substantial for the octopus sign (kappa = 0.747). Significant differences in distribution of the octopus sign between stages 2 and 3 were found with more frequent octopus signs in stage 2 and fewer in stage 3. In addition, we only found the octopus sign in cases of nodular und cystic lung disease. Conclusions: The octopus sign in PLCH can be identified not only on histological images, but also on HRCT images. Its radiological presence seems to depend on the stage of PLCH

Improved exercise ventilatory efficiency with nasal compared to oral breathing in cardiac patients.

Objectives: To assess whether nasal breathing improves exercise ventilatory efficiency in patients with heart failure (HF) or chronic coronary syndromes (CCS). Background: Exercise inefficient ventilation predicts disease progression and mortality in patients with cardiovascular diseases. In healthy people, improved ventilatory efficiency with nasal compared to oral breathing was found. Methods: Four study groups were recruited: Patients with HF, patients with CCS, old (age≥45 years) and young (age 20-40 years) healthy control subjects. After a 3-min warm-up, measurements of 5 min with once nasal and once oral breathing were performed in randomized order at 50% peak power on cycle ergometer. Ventilation and gas exchange parameters measured with spiroergometry were analysed by Wilcoxon paired-sample tests and linear mixed models adjusted for sex, height, weight and test order. Results: Groups comprised 15 HF, CCS, and young control and 12 old control. Ventilation/carbon dioxide production ( E/ CO2), ventilation ( E), breathing frequency (fR), and end-tidal oxygen partial pressure (PETO2) were significantly lower and tidal volume and end-tidal carbon dioxide partial pressure (PETCO2) significantly higher during nasal compared to oral breathing in all groups, with large effect sizes for most parameters. For patients with HF, median E/ CO2 was 35% lower, fR 26% lower, and PETCO2 10% higher with nasal compared to oral breathing, respectively. Exercise oscillatory ventilation (EOV) was present in 6 patients and markedly reduced with nasal breathing. Conclusion: Nasal breathing during submaximal exercise significantly improved ventilatory efficiency and abnormal breathing patterns (rapid shallow breathing and EOV) in 80% of our patients with HF and CCS

Azithromycin for the Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis: A Randomized Controlled Cross-over Trial.

RATIONALE Patients with idiopathic pulmonary fibrosis (IPF) frequently suffer from difficult to treat chronic cough, which substantially affects their quality of life. Azithromycin has been demonstrated to relieve chronic cough in some populations, however this has not been investigated in IPF. OBJECTIVES To determine the safety and efficacy of azithromycin for the treatment of chronic cough in patients with IPF. METHODS In a double-blind randomized controlled cross-over trial, patients with IPF underwent two 12-week intervention periods (azithromycin 500mg or placebo 3 times per week). The primary outcome was change in cough-related quality of life measured by the Leicester cough questionnaire (LCQ). Secondary outcomes included cough severity measured using Visual Analog Scale (VAS), health-related quality of life assessed by the St. George's Respiratory Questionnaire (SGRQ), and objective cough frequency using audiovisual readings from 24h respiratory polygraphy. RESULTS 25 patients were randomized (23 men, 2 women), 20 patients completed the study. Mean (standard deviation, SD) age was 67 (8) years, mean (SD) forced vital capacity (FVC) was 65 (16) %-predicted, and diffusion capacity (DLCO) 43 (16) %-predicted. Mean (SD) baseline LCQ was 11.7 (3.7) and 11.3 (3.3) for the azithromycin and the placebo period, respectively, and the corresponding mean (SD) cough VAS 5.6 (2.3) and 5.8 (2.1). There was no significant change in LCQ and VAS with azithromycin or placebo. Similarly, there was no significant difference in change in polygraphy measured cough frequency between the azithromycin and placebo periods. Gastrointestinal adverse effects were more frequent with azithromycin than with placebo (diarrhea 43% vs 5%, p=0.03). CONCLUSIONS This randomized controlled trial does not support the use of low dose azithromycin for chronic cough in patients with IPF. Clinical trial registered with ClinicalTrials.gov (NCT02173145)

Serum calprotectin as new biomarker for disease severity in idiopathic pulmonary fibrosis: a cross-sectional study in two independent cohorts

Background: Non-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity. Methods: Blood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels. Results: The IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47 +/- 1.67 vs 0.97 +/- 0.53 mu g/mL, p<0.001). In addition, serum calprotectin levels correlated with DLCO% predicted (r=-0.53, p=0.007) and with CPI (r=0.66, p=0.007). These findings were confirmed in an independent IPF validation cohort. Conclusion: Serum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF

Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis

BackgroundHigh bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown.MethodsWe sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR.ResultsAZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genusStreptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment inPrevotella.ConclusionsAZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites

Incidence and prognostic significance of hypoxemia in fibrotic interstitial lung disease: an international cohort study.

BACKGROUND Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD is currently unknown. RESEARCH QUESTION What are the epidemiology of hypoxemia and its additive prognostic value in current risk prediction model in fibrotic ILD? METHODS We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis (IPF)) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-minute walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality/transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the "ILD-GAP-O2" model), which included oxygenation status as a predictor. RESULTS The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1% for exertional hypoxemia, and 2.4%, 5.6%, and 16.5% for resting hypoxemia, which were significantly higher in IPF patients compared to non-IPF patients (p<0.001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality/transplantation prediction (p<0.001 for both). The ILD-GAP-O2 model had improved discrimination (C-index of 0.80 vs 0.75) and model fit (Akaike information criteria of 400 vs 422) in the validation cohort, with comparable calibration. INTERPRETATION IPF patients have higher cumulative incidence of exertional and resting hypoxemia than non-IPF patients. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD

Improved exercise ventilatory efficiency with nasal compared to oral breathing in cardiac patients

Objectives: To assess whether nasal breathing improves exercise ventilatory efficiency in patients with heart failure (HF) or chronic coronary syndromes (CCS).Background: Exercise inefficient ventilation predicts disease progression and mortality in patients with cardiovascular diseases. In healthy people, improved ventilatory efficiency with nasal compared to oral breathing was found.Methods: Four study groups were recruited: Patients with HF, patients with CCS, old (age≥45 years) and young (age 20–40 years) healthy control subjects. After a 3-min warm-up, measurements of 5 min with once nasal and once oral breathing were performed in randomized order at 50% peak power on cycle ergometer. Ventilation and gas exchange parameters measured with spiroergometry were analysed by Wilcoxon paired-sample tests and linear mixed models adjusted for sex, height, weight and test order.Results: Groups comprised 15 HF, CCS, and young control and 12 old control. Ventilation/carbon dioxide production (V˙E/V˙CO2), ventilation (V˙E), breathing frequency (fR), and end-tidal oxygen partial pressure (PETO2) were significantly lower and tidal volume and end-tidal carbon dioxide partial pressure (PETCO2) significantly higher during nasal compared to oral breathing in all groups, with large effect sizes for most parameters. For patients with HF, median V˙E/V˙CO2 was 35% lower, fR 26% lower, and PETCO2 10% higher with nasal compared to oral breathing, respectively. Exercise oscillatory ventilation (EOV) was present in 6 patients and markedly reduced with nasal breathing.Conclusion: Nasal breathing during submaximal exercise significantly improved ventilatory efficiency and abnormal breathing patterns (rapid shallow breathing and EOV) in 80% of our patients with HF and CCS

Long-term outcome of patients with combined post- and pre-capillary pulmonary hypertension

Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients