Charlene D. Fell

Clinical Predictors of a Diagnosis of Idiopathic Pulmonary Fibrosis

RATIONALE Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias (IIPs) have similar clinical and radiographic features, but their histopathology, response to therapy, and natural history differ. A surgical lung biopsy is often required to distinguish between these entities. OBJECTIVES We sought to determine if clinical variables could predict a histopathologic diagnosis of IPF in patients without honeycomb change on high-resolution computed tomography (HRCT). METHODS Data from 97 patients with biopsy-proven IPF and 38 patients with other IIPs were examined. Logistic regression models were built to identify the clinical variables that predict histopathologic diagnosis of IPF. MEASUREMENTS AND MAIN RESULTS Increasing age and average total HRCT interstitial score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex, pulmonary function, presence of desaturation, or distance walked during a 6-minute walk test did not help discriminate pulmonary fibrosis from other IIPs. CONCLUSIONS Clinical data may be used to predict a diagnosis of IPF over other IIPs. Validation of these data with a prospective study is needed.

The Prognostic Value of Cardiopulmonary Exercise Testing in Idiopathic Pulmonary Fibrosis

RATIONALE Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. OBJECTIVES To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. METHODS Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. MEASUREMENTS AND MAIN RESULTS Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10-9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. CONCLUSIONS We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.

Idiopathic Pulmonary Fibrosis: Phenotypes and Comorbidities

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease of the lung with an unknown etiology and limited treatment options. Three distinct phenotypes of IPF have been proposed: combined pulmonary fibrosis and emphysema, disproportionate pulmonary hypertension in IPF, and rapidly progressive IPF. Although treatment options for IPF are limited, much can be done to identify and alleviate symptoms from comorbidities, potentially improving the overall quality of life and well-being of these patients. This article describes emerging evidence to support the hypothesis that there is more than one phenotype for IPF and describes the common comorbidities seen in this disease.

Sex differences in physiological progression of idiopathic pulmonary fibrosis.

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.

Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada

Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation. We used mandatory national administrative data from 2007–2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life. For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease. Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited. National data for 100% of admissions in Canada show higher prevalence and incidence of IPF than in other countries http://ow.ly/4mTVQD

Pulmonary manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized serologically by an autoantibody response to nucleic antigens, and clinically by injury and/or malfunction in any organ system. During their disease course, up to 50% of SLE patients will develop lung disease. Pulmonary manifestations of SLE include pleuritis (with or without effusion), inflammatory and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, pulmonary hypertension, airways disease, and thromboembolic disease. Two major themes inform our understanding of SLE-associated pulmonary manifestations: first, the presence of specific autoantibodies correlates with the presence of certain pulmonary manifestations and second, vascular injury marks a common pathophysiologic thread among the various SLE-related lung diseases. This review will focus on the clinical presentation, pathogenesis, pathology, management, and prognosis of these SLE-associated lung conditions.

Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis

BACKGROUND: The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. METHODS: Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed‐effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. RESULTS: Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow‐up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) % predicted were declining at a mean rate of 0.12% (P < .001) and 0.10% (P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% (P = .103) and Dlco increased by 3.9% (P < .001). CONCLUSIONS: Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.

Smoking-related idiopathic interstitial pneumonia

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11–0.21), among the pathologists 0.36 (95% CI 0.32–0.40) and among the radiologists 0.43 (95% CI 0.35–0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease. Associations between smoking and ILD are largely nonspecific, but a small group may have smoking-related ILD http://ow.ly/wExAf

Supplemental Oxygen in Interstitial Lung Disease: An Art in Need of Science

&NA; Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in patients with advanced lung disease with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial. In some regions, the lack of robust data creates barriers to funding support and access to supplemental oxygen for patients with ILD. Further research into the role of oxygen supplementation is needed to optimize the comprehensive care of this patient population.

Safety of Nintedanib Added to Pirfenidone Treatment for Idiopathic Pulmonary Fibrosis

We assessed safety and tolerability of treatment with pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day−1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF. Combined pirfenidone and nintedanib was tolerated by the majority of patients with IPF, encouraging further study http://ow.ly/1Iq030kaZuD