Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study).

BACKGROUND: There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. METHODS: The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. RESULTS: We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan-Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622-54,287) and the median annual cost per patient was €18,362 (6856-52,026), of which €11,784 (3003-42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. CONCLUSIONS: This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842.

Opportunities to diagnose fibrotic lung diseases in routine care: A primary care cohort study.

BACKGROUND AND OBJECTIVE: Temporal trends of healthcare use in the period before a diagnosis of pulmonary fibrosis are poorly understood. We investigated trends in respiratory symptoms and LR HRU in the 10 years prior to diagnosis. METHODS: We analysed a primary care clinical cohort database (UK OPCRD) and assessed patients aged ≥40 years who had an electronically coded diagnosis of pulmonary fibrosis between 2005 and 2015 and a minimum 2 years of continuous medical records prior to diagnosis. Exclusion criteria consisted of electronic codes for recognized causes of pulmonary fibrosis such as CTD, sarcoidosis or EAA. RESULTS: Data for 2223 patients were assessed. Over the 10 years prior to diagnosis of pulmonary fibrosis, there was a progressive increase in HRU across multiple LR-related domains. Five years before diagnosis, 18% of patients had multiple healthcare contacts for LR complaints; this increased to 79% in the year before diagnosis, with 38% of patients having five or more healthcare contacts. CONCLUSION: There are opportunities to diagnose pulmonary fibrosis at an earlier stage; research into case-finding algorithms and strategies to educate primary care physicians is required.

Computed Tomography Honeycombing Identifies a Progressive Fibrotic Phenotype with Increased Mortality across Diverse Interstitial Lung Diseases.

Rationale: Honeycombing on chest computed tomography (CT) has been described in diverse forms of interstitial lung disease (ILD); however, its prevalence and association with mortality across the spectrum of ILD remains unclear. Objective: To determine the prevalence and prognostic value of CT honeycombing and characterize associated mortality patterns across diverse ILD subtypes in a multicenter cohort. Methods: This was an observational cohort study of adult participants with multidisciplinary or adjudicated ILD diagnosis and documentation of chest CT imaging at index diagnosis across five U.S. hospitals (one tertiary and four nontertiary medical centers). Participants were stratified based on presence or absence of CT honeycombing. Vital status was determined from review of medical records and social security death index. Transplant-free survival was analyzed using univariate and multivariable Cox regression. Results: The sample comprised 1,330 participants (mean age, 66.8 yr; 50% men) with 4,831 person-years of follow-up. The prevalences of CT honeycombing were 42.0%, 41.9%, 37.6%, and 28.6% in chronic hypersensitivity pneumonitis, connective tissue disease-related ILD (CTD-ILD), idiopathic pulmonary fibrosis (IPF), and unclassifiable/other ILDs, respectively. Among those with CT honeycombing, cumulative mortality hazards were similar across ILD subtypes, except for CTD-ILD, which had a lower mortality hazard. Overall, the mean survival time was shorter among those with CT honeycombing (107 mo; 95% confidence interval [CI], 92-122 mo) than those without CT honeycombing (161 mo; 95% CI, 147-174 mo). CT honeycombing was associated with an increased mortality rate (hazard ratio, 1.72; 95% CI, 1.38-2.14) even after adjustment for center, sex, age, forced vital capacity, diffusing capacity, ILD subtype, and use of immunosuppressive therapy (hazard ratio, 1.62; 95% CI, 1.29-2.02). CT honeycombing was associated with an increased mortality rate within non-IPF ILD subgroups (chronic hypersensitivity pneumonitis, CTD-ILD, and unclassifiable/other ILD). In IPF, however, mortality rates were similar between those with and without CT honeycombing. Conclusions: CT honeycombing is prevalent in diverse forms of ILD and uniquely identifies a progressive fibrotic ILD phenotype with a high mortality rate similar to IPF. CT honeycombing did not confer additional risk in IPF, which is already known to be a progressive fibrotic ILD phenotype regardless of the presence of CT honeycombing.

Progressive Massive Fibrosis Resurgence Identified in U.S. Coal Miners Filing for Black Lung Benefits, 1970-2016.

RATIONALE: There has been a resurgence of progressive massive fibrosis (PMF) in the United States, particularly among central Appalachian miners. OBJECTIVES: We characterized the proportion of PMF among former U.S. coal miners applying for Federal Black Lung Program benefits, 1970-2016. METHODS: Data from the U.S. Department of Labor were used to characterize trends in proportion of PMF cases, defined as an approved black lung claim with a determination of PMF, among all miners who filed for federal benefits between January 1, 1970, and December 31, 2016. Joinpoint, logistic, and linear regression models were used to identify changes in the proportion of claimants with PMF over time. RESULTS: There were 4,679 unique PMF cases among claimants for federal black lung benefits between 1970 and 2016, with 2,474 miners determined to have PMF since 1996. The number of PMF cases among Federal Black Lung Program claimants fell from 404 (0.5% of claimants) in 1978 to a low of 18 cases (0.6%) in 1988, and then increased to 353 cases (8.3%) in 2014. The proportion of federal black lung benefits claimants with PMF has been increasing since 1978 (0.06% annual percent change [APC]; 95% confidence interval [CI], 0.05-0.07%; P < 0.0001), and began increasing at a significantly increased rate after 1996 (0.26% APC; 95% CI, 0.25-0.28%; P < 0.0001). Most miners with PMF (84%) last mined in West Virginia, Kentucky, Pennsylvania, or Virginia. Since 1970, the proportion of claimants with PMF has increased significantly among miners who last worked in Kentucky (16.6% APC; 95% CI, 16.5-16.7%), Pennsylvania (4.7% APC; 95% CI, 4.6-4.8%), Tennessee (16.1% APC; 95% CI, 15.7-16.4%), West Virginia (16.8% APC; 95% CI, 16.6-16.9%), and most sharply among miners last working in Virginia (31.5% APC; 95% CI, 31.2-31.7%), where in 2009, more than 17% of claimants received a PMF determination. The proportion of PMF determinations for the rest of the United States has not exceeded 4%. CONCLUSIONS: There has been a resurgence of PMF, particularly in central Appalachian miners. The resurgence of this preventable disease points to the need for improved primary and secondary prevention of dust-related lung disease in U.S. coal miners.

Disparities in pulmonary fibrosis care in the United States: an analysis from the Nationwide Inpatient Sample.

BACKGROUND: Idiopathic pulmonary fibrosis is a disease with high morbidity and mortality. Care for these patients, including lung transplantation, may provide significant benefits, but is resource-intensive and expensive. Disadvantaged patients with IPF may hence be at risk for receiving inferior care. METHODS: We analyzed data from the Nationwide Inpatient Sample, a database consisting of all hospitalizations from a 20% sample of US hospitals. We identified adults hospitalized with IPF between 1998 and 2011 using ICD-9 codes. We assessed the effect of insurance coverage and socioeconomic status (SES) on lung transplantation, a treatment that may improve survival. We also examined the effect of coverage and SES on mortality, as well as discharge to inpatient rehabilitation and receipt of a lung biopsy, two markers of the intensity of care delivered. We used multiple logistic regression to adjust for patient and hospital characteristics. RESULTS: We identified 148,877 hospitalizations that met our definition of pulmonary fibrosis. In the main adjusted analyses, hospitalizations of patients with Medicaid (OR 0.30, 95% CI 0.16-0.57) or no insurance (OR 0.22, 95% CI 0.07-0.72) were less likely to result in a lung transplantation compared to hospitalizations of those with non-Medicaid insurance. Those of lower SES were also less likely to undergo transplantation, while hospitalized patients with Medicaid and the uninsured were less likely to be discharged to inpatient rehabilitation or to receive a lung biopsy. CONCLUSIONS: Among hospitalized patients with IPF, those with lower SES, Medicaid coverage and without insurance were less likely to receive several clinical interventions.

A systematic review of validated methods for identifying pulmonary fibrosis and interstitial lung disease using administrative and claims data.

PURPOSE: The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease. METHODS: PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms. RESULTS: Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used. CONCLUSIONS: Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity.

Lung transplantation in the United States, 1998-2007.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Single versus double lung transplantation in pulmonary fibrosis: a debated topic.

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

Health-related quality of life in patients with idiopathic pulmonary fibrosis--cross-sectional and longitudinal study.

OBJECT: To validate the cross-sectional and longitudinal use of the Medical Outcome Study Short Form 36 (SF-36) for measuring health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients were administered the SF-36 and concomitantly underwent laboratory and physiologic tests and high-resolution computed tomography (HRCT). Forty-six patients participated in the initial cross-sectional study, and 32 patients who were available more than one year later again underwent these studies under the same conditions. RESULTS: Patients with IPF had significantly lower scores across all 8 domains of the SF-36 when compared with the general population. Significant decline of HRQL was observed in 2 physical domains. There were significant differences in within-subject changes in a few domains according to worsening of the physiologic parameters. Vital capacity as percent of predicted was significantly correlated with the results of 6 subscales and its changes were significantly correlated with those of 4 subscales. The 6-min-walk distance was correlated significantly with 3 subscales and its changes were significantly correlated with those of 4 subscales. Changes in the HRCT ground-glass score were significantly correlated with those of 3 subscales. No significant correlations between changes in 3 domains and those of any clinical parameters were observed. CONCLUSION: Patients with IPF had significantly impaired HRQL in both physical and psychological functions. This disease clearly decreased the physical aspects of HRQL over time. HRQL instruments should be incorporated into routine evaluations of IPF patients, since they measure dimensions not fully estimated by clinical assessment.

Assessing the burden of respiratory disease in the UK.

This review explores the health and social burden of some of the main respiratory diseases (asthma, chronic obstructive pulmonary disease, cryptogenic fibrosing alveolitis, cystic fibrosis, lung cancer, mesothelioma, obstructive sleep apnoea and tuberculosis) in order to increase awareness of these diseases and highlight areas where improvements in care are required. The overall impact of respiratory diseases in the U.K. in terms of prevalence, mortality, morbidity and economic costs, with particular reference to secondary care has been considered and comparisons made with the rest of Europe where data are available. Respiratory diseases are responsible for a significant proportion of serious morbidity and premature death among the population of the U.K. and they will continue to present a growing challenge; special support is needed to tackle this burden.

Coal dust exposures in the longwall mines of New South Wales, Australia: a respiratory risk assessment.

This paper presents an analysis of personal respirable coal dust measurements recorded by the Joint Coal Board in the underground longwall mines of New South Wales from 1985 to 1999. A description of the longwall mining process is given. In the study, 11 829 measurements from 33 mines were analysed and the results given for each occupation, for seven occupational groups, for individual de-identified mines and for each year of study. The mean respirable coal dust concentration for all jobs was 1.51 mg/m(3) (SD 1.08 mg/m(3)). Only 6.9% of the measurements exceeded the Australian exposure standard of 3 mg/m(3). Published exposure-response relationships were used to predict the prevalence of progressive massive fibrosis and the mean loss of FEV(1), after a working lifetime (40 years) of exposure to the mean observed concentration of 1.5 mg/m(3). Prevalences of 1.3 and 2.9% were predicted, based on data from the UK and the USA, respectively. The mean loss of FEV(1) was estimated to be 73.7 ml.

Noncancer inhalation toxicology of crystalline silica: exposure-response assessment.

Silicosis from inhalation of silica has long been recognized as an occupational hazard. Concern has arisen regarding the potential risk of silicosis from ambient silica (primarily quartz dust). This presentation reviews available data regarding ambient silica levels and estimates of the risk of silicosis at low exposure levels as they relate to the current U.S. Environmental Protection Agency National Ambient Air Quality Standards (NAAQS) for particulate matter. Current data indicate that for individuals not compromised by other respiratory ailments and for ambient environments expected to sustain 10% or less silica fraction in particulate matter with a mean aerodynamic diameter of < or = 10 microns (PM10), maintenance of the 50 micrograms/m3 annual NAAQS for PM10 is adequate to protect against fibrotic effects from ambient silica exposures. Issues such as the large divergence of risk estimates within the occupational setting (particularly at high cumulative exposures) and factors to consider for extrapolating risk in an occupational setting to risk from ambient exposure are discussed.

[A retrospective assessment of 19 subjects compensated for the inhalation of aluminum powders (item 48, D.P.R. 482/75)]. / Valutazione retrospettiva su 19 soggetti indennizzati per inalazione di polveri di alluminio (voce 48, D.P.R. 482/75).

A study was made of 19 male subjects, mean age 54.7, S.D. 7.5 years, exposed to risk of aluminium dust inhalation for 16, S.D. 9.7 years, awarded compensation by the local provincial branch of INAIL (National Institute for Insurance against Occupational Accidents) in the period 1975-1988, as prescribed by item 48 of Presidential Decree 482/1975. The workers were divided into two groups on the basis of radiological signs of lung fibrosis (3 1/1 cases and 7 1/0 cases according to the ILO classification) or of COPD (Chronic Obstructive Pulmonary Disease) (9 cases). Careful examination of the work histories confirmed the previous observations of aluminium pneumoconiosis with moderate functional alterations in alumina production, potroom and casting workers.

Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL Cooperative Group Steering Committee.

The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)

The occupational history in the primary care setting.

PURPOSE: To assess the need for services in occupational medicine, we determined the prevalence of reported occupational exposures in patients seen in the primary care setting. In addition, we evaluated the validity of our survey instrument. PATIENTS AND METHODS: All patients (n = 1,112) seen over a 3-month period of time in the Primary Care Clinic at the Iowa City Veterans Affairs Medical Center were considered eligible for this study. A survey instrument was developed to obtain specific information regarding occupational exposures. The questionnaire was administered to 534 or 48% of all eligible patients. The validity of the survey instrument was evaluated by comparing chest radiographs in subjects with a history of exposure to asbestos, coal dust, or silica to those in patients who were not exposed to any of these agents. RESULTS: We found that almost 75% of the patients reported prior occupational exposure to at least one potentially toxic agent, and over 30% claimed exposure to at least four potentially toxic agents. The validation study indicated that the reported exposure history for asbestos, coal dust, and silica is significantly associated with anticipated changes on chest radiographs. These findings suggest that this easily administered survey instrument is valid for pneumoconiotic dust exposures and may also be valid for other potentially toxic exposures. CONCLUSION: Data from our study indicate that patients seen in the ambulatory care setting may have clinically significant occupational exposures that are relevant to their medical condition.

Epidemiological and clinical study of tuberculosis in the district of Kolín, Czechoslovakia. Second report (1965-1972).

An epidemiological and clinical study of tuberculosis in a district with a population of 100 000 has been in operation in Czechoslovakia since 1960. Its objective is to ascertain the epidemiological situation and long-term trend in respect of tuberculosis in a country with well-established tuberculosis control facilities. This second report presents the results achieved in the period 1965-72 and the epidemiological trend of tuberculosis observed during the 12-year study period. The fundamental control measures adopted during the study included systematic BCG vaccination of the newborn and revaccination of persons aged 14 and 19 years; mass surveys of the population over 14 years of age by photofluorography; case-finding among persons with symptoms and in risk groups; systematic treatment of all persons with active tuberculosis-i.e., supervised inpatient treatment followed by outpatient self-administered regimens; and radiological and bacteriological follow-up of cases.The results confirmed that the systematic application of effective treatment throughout the study population was followed by a rapid decline in the prevalence of bacillary tuberculosis, particularly in its chronic form. The incidence of bacillary tuberculosis declined more slowly, because the risk of contracting the disease continued to be high for middle-aged and elderly persons. Indiscriminate photofluorographic surveys of the study population at 3-yearly intervals produced a decreasing yield.An increasing proportion of noninfected persons among the population is the basic condition for a further decline of tuberculosis. The cost of tuberculosis control can be reduced by strict adherence to rational and economical working methods. Most of the economic indicators analysed fell to less than one-fifth between 1961 and 1972.