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Background Hospitalizations are common among patients with idiopathic pulmonary fibrosis (IPF). We investigated the impact of hospitalizations on outcomes in patients with IPF. Methods The IPF-PRO Registry is an observational US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Associations between patient characteristics and hospitalization, and between hospitalization and mortality, were analyzed using Cox regression models. Results A total of 1002 patients with IPF were enrolled into the IPF-PRO Registry. Over a median follow-up time of 23.7 months (maximum: 67.0 months), 568 patients (56.7%) had at least one hospitalization. Of these patients, 319 (56.2%) had at least one respiratory-related hospitalization and 120 (21.1%) had at least one hospitalization with ventilatory support. Younger age (HR 0.68 [95% CI 0.55, 0.84] per 5-year increase for patients Conclusions Data from the IPF-PRO Registry demonstrate that hospitalizations are common among patients with IPF. The risk of mortality during hospitalization or within 90 days of discharge was high, particularly among patients who were hospitalized for a respiratory cause or received ventilatory support. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

Rationale Two antifibrotic medications, nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the US. Few data have been published on the use of these medications in clinical practice. Objective To investigate patterns of use of antifibrotic medications in the US. Methods The IPF-PRO Registry, a multicenter US registry, has enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Data from patients enrolled from 5 June 2014 to 4 March 2018 were used to determine antifibrotic medication use ("treatment") in the enrollment window and a follow-up window approximately 6 months later. Associations between patient characteristics and treatment status were tested using logistic regression. Results Overall, 551 of 782 eligible patients (70.5%) were treated in the enrollment window. Younger age, lower FVC % predicted, oxygen use with activity, worse self-rated health based on the Short Form-12 (SF-12) or St George's Respiratory Questionnaire score, referral to the enrolling center by a pulmonologist, use of lung biopsy in diagnosis, and carrying a diagnosis of IPF to the enrolling center were associated with being treated. Among 534 patients treated at enrollment who had follow-up data, 94.0% remained treated in follow-up. Better self-rated health based on the SF-12 mental component score or EuroQoL score, and not using oxygen with activity at enrollment, were associated with continuing treatment in follow-up. Among 172 patients who were untreated at enrollment and had follow-up data, 29.7% started treatment in follow-up. Lower DLco % predicted, a family history of ILD, a history of sleep apnea, and a definite diagnosis of IPF at enrollment were associated with starting treatment in follow-up. Conclusions The majority of patients in the IPF-PRO Registry were receiving an approved medication for IPF at enrollment. Treatment at enrollment was associated with greater disease severity, more compromised quality of life and the use of oxygen with activity. Clinical trial registered with ClinicalTrials.gov (NCT01915511).

Background Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow–derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis. Methods Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 10 6 human bone marrow–derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression. Results No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide. Conclusions Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF. Trial Registry ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005–2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p

Obstructive sleep apnea (OSA) is a chronic and heterogeneous disorder that leads to early mortality, stroke, and cardiovascular disease (CVD). OSA is defined by the apnea-hypopnea index, which is an index of OSA severity that combines apneas (pauses in breathing) and hypopneas (partial obstructions in breathing) associated with hypoxemia. Yet, other sleep metrics (i.e., oxygen nadir, arousal frequency), along with clinical symptoms and molecular markers could be better predictors of stroke and CVD outcomes in OSA. The recent focus on personalized medical care introduces the possibility of a unique approach to the treatment of OSA based on its phenotypes, defined by pathophysiological mechanisms and/or clinical presentation. We summarized what is known about OSA and its phenotypes, and review the literature on factors or intermediate markers that could increase stroke risk and CVD in patients with OSA. The OSA phenotypes where divided across three different domains (1) clinical symptoms (i.e., daytime sleepiness), (2) genetic/molecular markers, and (3) experimental data-driven approach (e.g., cluster analysis). Finally, we further highlight gaps in the literature framing a research agenda.

Background Sirolimus (SIR) has been shown to stabilize the lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, there is no long-term data on the prophylactic use of SIR in lung transplant recipients. This retrospective study examines the effects of SIR in the prevention of BOS. Methods From 1999 to 2009, 24 lung transplant recipients whose maintenance immunosuppression regimen consisted of tacrolimus (Tac), mycophenolate mofetil (MMF) or azathioprine (AZA), and prednisone (Pred), were switched to Tac, SIR, and Pred at 1 year after transplantation. From these 24 patients, 5 developed side effects that necessitated the cessation of SIR within 1 year, while 19 patients tolerated long-term use of SIR. The clinical outcomes of these 19 patients (SIR group) were compared with 22 lung transplant recipients whose immunosupression regimen consisted of Tac, MMF or AZA, and Pred from the time of transplant (MMF group). Survival rates and freedom from BOS were calculated by the Kaplan-Meier method. Results The SIR group had a lower incidence of BOS and viral infection ( p = 0.05), and higher survival rates ( p = 0.004). The SIR group had lower levels of Tac and received less Pred. The incidences of acute rejection, carcinoma, hypertension, and diabetes were similar between both groups. Conclusions Results from this study suggest that conversion to SIR 1 year after lung transplantation improves survival and decreases the development of BOS. Randomized studies with higher number of patients are needed to determine the prophylactic efficacy of sirolimus in preventing the development of BOS.

Introduction Estimating the clinical probability of mediastinal metastasis in patients with non-small cell lung cancer (NSCLC) can facilitate the selection and interpretation of staging tests. Purpose We sought to identify independent clinical predictors of mediastinal metastasis and to develop a prediction rule to estimate the pretest probability of nodal metastasis in patients with NSCLC. Methods We used data from a randomized controlled trial of selective versus routine mediastinoscopy to develop a clinical prediction model. Results Five hundred sixty-six patients were included, with a mean age of 65 ± 9 years; 31% had positive lymph nodes. Independent predictors of positive nodes included adenocarcinoma or large cell histology (OR 2.6, 95% confidence interval [CI] = 1.8–3.9), apparent metastatic disease on chest radiography (OR 2.4, 95% CI=1.2–4.7), central location of the primary tumor (OR 2.1, 95% CI=1.4–3.3), symptoms from the primary tumor (OR 1.6, 95% CI=1.1–2.4), tumor diameter ≥3.6 cm (OR 1.5, 95% CI=1.0–2.3), and age less than 65 years (OR 1.5, 95% CI=1.0–2.2). Model accuracy and calibration were good, with an area under the receiver operating characteristic curve of 0.70 (95% CI=0.66–0.75) and good agreement between observed and predicted probabilities of mediastinal metastasis. Conclusions Our prediction rule can be used to estimate the pretest probability of mediastinal metastasis in patients with NSCLC. Such estimates can facilitate clinical decision making when selecting and interpreting the results of noninvasive and invasive staging tests.

Source Citation Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for obstructive sleep apnea in adults: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:407-14. ...

Poor adherence undermines the effectiveness of positive airway pressure (PAP) therapy for sleep apnea. Disparities exist in PAP adherence by race/ethnicity and neighborhood socioeconomic status (SES), but the etiology of these differences is poorly understood. We investigated whether home environmental factors contribute to PAP adherence and whether identified factors explain disparities in adherence by SES.Adult patients with sleep apnea were surveyed at clinic visits about their sleep environment. Medical records were abstracted for demographic data, sleep apnea severity, comorbidities, and objective PAP adherence. We evaluated the association between aspects of home sleep environment with PAP adherence using multivariate linear and logistic regression, and assessed effect modification by SES factors.Participants (n = 119) were diverse, with 44% nonwhite and 35% uninsured/Medicaid. After adjusting for age, sex, race/ethnicity, insurance, neighborhood SES, education, and marital status, participants who endorsed changing sleeping location once per month or more (18%, n = 21) had 77% lower odds of meeting PAP adherence criteria (4 h/night for 70% of nights) and less PAP use (median -11 d/mo, 95% confidence intervals -15.3, -6.5). Frequency of sleeping location change was the only environmental factor surveyed associated with PAP adherence.Frequent change in sleeping location is associated with reduced PAP adherence, independent of sociodemographic factors. This novel finding has implications for physician-patient dialogue. PAP portability considerations in device selection and design may modify adherence and potentially improve treatment outcomes. Prospective investigation is needed to confirm this finding and inform design of possible interventions.

Is continuous positive airway pressure (CPAP) therapy better than no therapy in reducing the incidence of hypertension or cardiovascular (CV) events in a cohort of nonsleepy patients with obstructive sleep apnea (OSA)?Randomized, controlled trial; no placebo CPAP used. ClinicalTrials.gov Identifier: NCT00127348.Randomization was performed using a computer generated list of random numbers in the coordinating center and results were mailed to participating centers in numbered opaque envelopes.Primary outcome was evaluated by individuals not involved in the study and who were blinded to patient allocation. Patients, investigators, and the statistician were not blinded.median 4 (interquartile range, 2.7-4.4) years.14 academic medical centers in Spain.725 adults (mean age 51.8 y, 14% women) who were diagnosed with OSA with apnea hypopnea index (AHI) ≥ 20 events per hour and Epworth sleepiness score (ESS) ≤ 10 were randomized. Subjects with previous CV events were excluded. However, patients with a history of hypertension were not excluded (50% of the sample were hypertensive at baseline).Patients were randomized to receive CPAP treatment or no active intervention. All participants received dietary counseling and advice about sleep hygiene.The primary outcome was the incidence of either systemic hypertension (among participants who were normotensive at baseline) or CV events (among all participants). The secondary outcome was the association between the incidence of hypertension or CV events (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, and CV death) and the severity of OSA assessed by the AHI and oxygen saturation. The sample size was calculated assuming that the incidence of hypertension or new CV event in this population over a period of 3 years would be 10% annually; 345 patients per group were needed to detect a 60% reduction in incidence of new hypertension or CV events (90% power, 2-sided α = 0.05, assuming 10% study dropout).83% complete (only patients who received the allocated intervention were included in analysis of primary outcome).A total of 147 patients with new hypertension and 59 cardiovascular events were identified (Table). In the CPAP group, there were 68 patients with incident hypertension and 28 CV events. Of the 357 participants in the CPAP group, 127 used CPAP4 hours/night (36%). In the control group, there were 79 patients with new hypertension and 31 CV events. There was no statistically significant difference between the groups in the primary outcome. TableRisk for incident hypertension or cardiovascular eventIn adults with moderate to severe OSA and no symptoms of daytime sleepiness, CPAP therapy did not reduce incident hypertension or CV event compared with no active therapy.Instituto de Salud Carlos III (PI 04/0165) (Fondo de Investigaciones Sanitarios, Ministerio de Sanidad y Consumo, Spain), Spanish Respiratory Society (SEPAR) (Barcelona), Resmed (Bella Vista, Australia), Air Products-Carburos Metalicos (Barcelona), Respironics (Murrysville, Pennsylvania), and Breas Medical (Madrid, Spain).

Background and Purpose Sleep-related falling out of bed (SFOB), with its potential for significant injury, has not been a strong focus of investigation in Parkinson's disease (PD) to date. We describe the demographic and clinical characteristics of PD patients with and without SFOB. Methods We performed a retrospective analysis of 50 consecutive PD patients, who completed an REM sleep behavior disorder screening questionnaire (RBDSQ), questionnaires to assess for RBD clinical mimickers and questions about SFOB and resulting injuries. Determination of high risk for RBD was based on an RBDSQ score of 5 or greater. Results Thirteen patients reported history of SFOB (26%). Visual hallucinations, sleep-related injury, quetiapine and amantadine use were more common in those patients reporting SFOB. Twenty-two patients (44%) fulfilled criteria for high risk for RBD, 12 of which (55%) reported SFOB. Five patients reported injuries related to SFOB. SFOB patients had higher RBDSQ scores than non-SFOB patients (8.2±3.0 vs. 3.3±2.0, p

Source Citation Drager LF, Brunoni AR, Jenner R, et al. Effects of CPAP on body weight in patients with obstructive sleep apnoea: a meta-analysis of randomised trials. Thorax. 2014 Nov 28. [Epub ah...

Source Citation Keenan SP, Sinuff T, Burns KE, et al. Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in th...

Source Citation Jaeschke R, O’Byrne PM, Mejza F, et al. The safety of long-acting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis. Am J Re...

Source Citation Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2007;(4):CD000567. 17943746