Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

Although these conditions are rare, a proportion of patients with interstitial lung diseases (ILDs) may develop a progressive-fibrosing phenotype. Progressive fibrosis is associated with worsening respiratory symptoms, lung function decline, limited response to immunomodulatory therapies, decreased quality of life and, potentially, early death. Idiopathic pulmonary fibrosis may be regarded as a model for other progressive-fibrosing ILDs. Here we focus on other ILDs that may present a progressive-fibrosing phenotype, namely idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, connective tissue disease-associated ILDs (e.g. rheumatoid arthritis-related ILD), fibrotic chronic hypersensitivity pneumonitis, fibrotic chronic sarcoidosis and ILDs related to other occupational exposures. Differential diagnosis of these ILDs can be challenging, and requires detailed consideration of clinical, radiological and histopathological features. Accurate and early diagnosis is crucial to ensure that patients are treated optimally

Predictors of Time to Death After Terminal Withdrawal of Mechanical Ventilation in the ICU

Little information exists about the expected time to death after terminal withdrawal of mechanical ventilation. We sought to determine the independent predictors of time to death after withdrawal of mechanical ventilation. METHODS: We conducted a secondary analysis from a cluster randomized trial of an end-of-life care intervention. We studied 1,505 adult patients in 14 hospitals in Washington State who died within or shortly after discharge from an ICU following terminal withdrawal of mechanical ventilation (August 2003 to February 2008). Time to death and its predictors were abstracted from the patients' charts and death certificates. Predictors included demographics, proxies of severity of illness, life-sustaining therapies, and International Classification of Diseases, 9th ed., Clinical Modification codes. RESULTS: The median (interquartile range [IQR]) age of the cohort was 71 years (58-80 years), and 44% were women. The median (IQR) time to death after withdrawal of ventilation was 0.93 hours (0.25-5.5 hours). Using Cox regression, the independent predictors of a shorter time to death were nonwhite race (hazard ratio [HR], 1.17; 95% CI, 1.01-1.35), number of organ failures (per-organ HR, 1.11; 95% CI, 1.04-1.19), vasopressors (HR, 1.67; 95% CI, 1.49-1.88), IV fluids (HR, 1.16; 95% CI, 1.01-1.32), and surgical vs medical service (HR, 1.29; 95% CI, 1.06-1.56). Predictors of longer time to death were older age (per-decade HR, 0.95; 95% CI, 0.90-0.99) and female sex (HR, 0.86; 95% CI, 0.77-0.97). CONCLUSIONS: Time to death after withdrawal of mechanical ventilation varies widely, yet the majority of patients die within 24 hours. Subsequent validation of these predictors may help to inform family counseling at the end of life.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85787/1/Cooke - Predictors of time to death after withdrawal.pd

Low Birth Weight and Respiratory Disease in Adulthood: A Population-based Case-Control Study

Rationale: The proportion of low and very low birth weight births is increasing. Infants and children with a history of low and very low birth weight have an increased risk of respiratory illnesses, but it is unknown if clinically significant disease persists into adulthood

Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis.

BackgroundNintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied.ObjectiveWe conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF.Methods113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory.ResultsAdjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: -9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: -1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were -14.2 mL and -83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: -8.7, 146.8]).ConclusionExploratory data suggest that in patients with IPF, 6 months' treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF

Defining the pathway to timely diagnosis and treatment of interstitial lung disease: a US Delphi survey

Introduction Timely diagnosis of interstitial lung disease (ILD) is limited by obstacles in the current patient pathway. Misdiagnosis and delays are common and may lead to a significant burden of diagnostic procedures and worse outcomes. This Delphi survey aimed to identify consensus on the key steps that facilitate the patient journey to an accurate ILD diagnosis and appropriate management in the US.Methods A modified Delphi analysis was conducted, comprising three online surveys based on a comprehensive literature search. The surveys spanned five domains (guidelines, community screening, diagnosis, management and specialist referral) and were completed by a panel of US physicians, including primary care physicians and pulmonologists practising in community or academic settings. A priori definitions of consensus agreement were median scores of 2–3 (agree strongly/agree), with an IQR of 0–1 for questions on a 7-point Likert scale from −3 to 3, or ≥80% agreement for binary questions.Results Forty-nine panellists completed the surveys and 62 statements reached consensus agreement. There was consensus agreement on what should be included in the primary care evaluation of patients with suspected ILD and the next steps following workup. Regarding diagnosis in community pulmonology care, consensus agreement was reached on the requisition and reporting of high-resolution CT scans and the appropriate circumstances for holding multidisciplinary discussions. Additionally, there was consensus agreement on which symptoms and comorbidities should be monitored, the frequency of consultations and the assessment of disease progression. Regarding specialist referral, consensus agreement was reached on which patients should receive priority access to ILD centres and the contents of the referral package.Conclusions These findings clarify the most common issues that should merit further evaluation for ILD and help define the steps for timely, accurate diagnosis and appropriate collaborative specialty management of patients with ILD

Associations between Patient-reported Outcomes and Death or Lung Transplant in Idiopathic Pulmonary Fibrosis. Data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry

Progression of idiopathic pulmonary fibrosis (IPF) is accompanied by worsening of symptoms, exercise capacity, and health-related quality of life. However, the utility of patient-reported outcomes as predictors of mortality remains uncertain. To assess whether patient-reported outcomes are independently associated with mortality beyond clinical risk factors in patients with IPF. Data from the observational IPF Prospective Outcomes Registry were used to examine associations between patient-reported outcomes at enrollment and the composite outcome of death or lung transplant in the following year. Associations were examined using univariable models and models adjusted for age and clinical variables that have been associated with death or lung transplant in patients with IPF in this cohort (oxygen use, forced vital capacity % predicted, and diffusing capacity of the lungs for carbon monoxide % predicted at enrollment). Among 662 patients, 45 died and 12 underwent lung transplant over 1 year. In the model adjusted for age and clinical variables that were associated with death or lung transplant, worse scores on the St. George's Respiratory Questionnaire (SGRQ) total score (hazard ratio [HR], 1.22 [95% confidence interval (CI), 1.01-1.48] per 10-point increase), SGRQ activity score (HR, 1.25 [95% CI, 1.02-1.54] per 10-point increase) and SGRQ symptoms score (HR, 1.17 [95% CI, 1.01-1.36] per 10-point increase) were associated with death or lung transplant over 1 year. Patient-reported outcomes that assess symptoms and physical activity are independently associated with mortality in patients with IPF

Hospitalizations in patients with idiopathic pulmonary fibrosis

Abstract 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 < 62 years), lower BMI (0.96 [0.93, 0.98] per 1-point increase), lower FVC % predicted (0.90 [0.83, 0.97] per 10% increase), oxygen use at rest (2.85 [2.18, 3.72]) and history of pulmonary hypertension (2.02 [1.37, 2.96]) at enrollment were associated with an increased risk of respiratory-related hospitalization during follow-up. In a multivariable model, there was an eightfold increase in the risk of mortality during hospitalization or within 90 days of discharge compared with outside of this period. The risk of mortality associated with a respiratory hospitalization or a hospitalization with ventilatory support was even greater. 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/NCT0191551