Oesophageal diameter is associated with severity but not progression of systemic sclerosis-associated interstitial lung disease.

BACKGROUND AND OBJECTIVE: It is unknown whether oesophageal disease is associated with systemic sclerosis-associated interstitial lung disease (SSc-ILD) severity, progression or mortality. METHODS: High-resolution computed tomography (HRCT) scans from 145 SSc-ILD patients were scored for fibrosis score, oesophageal diameter and presence of hiatal hernia. Fibrosis asymmetry was calculated as: (most affected side - least affected side)/(most affected side + least affected side). Mixed effects models were used for repeated measures analyses. RESULTS: Mean fibrosis score was 8.6%, and most patients had mild-to-moderate physiological impairment. Every 1 cm increase in oesophageal diameter was associated with 1.8% higher fibrosis score and 5.5% lower forced vital capacity (FVC; P ≤ 0.001 for unadjusted and adjusted analyses). Patients with hiatal hernia had 3.9% higher fibrosis score, with persistent differences on adjusted analysis (P = 0.001). Oesophageal diameter predicted worsening fibrosis score over the subsequent year (P = 0.02), but not when adjusting for baseline fibrosis score (P = 0.16). Oesophageal diameter was independently associated with mortality (P = 0.001). Oesophageal diameter was not associated with asymmetric disease or radiological features of gross aspiration. CONCLUSION: Oesophageal diameter and hiatal hernia are independently associated with SSc-ILD severity and mortality, but not with ILD progression or asymmetric disease. Oesophageal disease is unlikely to be a significant driver of ILD progression in SSc.

Frailty is common and strongly associated with dyspnoea severity in fibrotic interstitial lung disease.

BACKGROUND AND OBJECTIVE: Frailty is the age-related accumulation of deficits that decrease the ability to respond to biological stress. Patients with fibrotic interstitial lung disease (ILD) may be frail due to consequences of ILD, age, co-morbidities and adverse effects of pharmacotherapies. The objective of this study was to examine the prevalence and predictors of frailty in fibrotic ILD. METHODS: Fibrotic ILD patients were recruited from a specialized clinic. Patients with ILD secondary to a systemic disease were excluded. Frailty was determined using the Frailty Index based on the presence or absence of multiple deficits, including co-morbidities, symptoms and functional limitations. The Frailty Index was based on the proportion of deficits present, with frailty defined as a score >0.21. Cronbach's alpha was used to estimate the internal consistency of the Frailty Index. Dyspnoea was measured using the University of California San Diego Shortness of Breath Questionnaire. Multivariate analysis was used to determine independent predictors of frailty. RESULTS: The definition of frailty was met in 50% of the 129 patients. Cronbach's alpha for the Frailty Index was 0.87. The Frailty Index was associated with forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1 ), diffusion capacity of the lung for carbon monoxide (DLCO ), ILD-gender, age and physiology (GAP) index, composite physiologic index and dyspnoea score. Dyspnoea severity was the strongest unadjusted predictor (r = 0.65, P < 0.001) and only independent predictor of the Frailty Index (0.034 increase in Frailty Index per 10-point increase in dyspnoea score; R2 = 0.37; P < 0.001). CONCLUSION: Frailty is highly prevalent and is strongly and independently associated with dyspnoea severity, demonstrating that dyspnoea is a more important determinant of frailty than pulmonary function.

Does Systemic Sclerosis-associated Interstitial Lung Disease Burn Out? Specific Phenotypes of Disease Progression.

RATIONALE: Previous studies have suggested that interstitial lung disease (ILD) progresses most rapidly early in the course of systemic sclerosis-associated (SSc)-ILD, and that SSc-ILD is often more stable or even "burned out" after the first 4 years following diagnosis. OBJECTIVES: Our objectives were to determine whether an apparent plateau in pulmonary function decline is due to survival bias and to identify distinct prognostic phenotypes of ILD progression. METHODS: Consecutive patients with SSc-ILD from a single center were included. Pulmonary function measurements were typically performed every 6 months. Study participants were categorized into long-term survivors (>8 yr survival from diagnosis), and those with medium-term and short-term mortality (4-8 and <4 yr survival, respectively). We excluded those censored with less than 8 years of follow-up. Subject-specific slopes for change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DlCO) were calculated using generalized linear models with mixed effects. The rate of decline in FVC was compared across prognostic groups. RESULTS: The cohort included 171 study participants with SSc-ILD. A plateau in the progression of FVC was apparent in the full cohort analysis but disappeared with stratification into prognostic subgroups to account for survival bias. Those with short-term mortality had a higher annual rate of decline in FVC (-4.10 [95% confidence interval (CI), -7.92 to -0.28] vs. -2.14 [95% CI, -3.31 to -0.97] and -0.94 [-1.46 to -0.42]; P = 0.003) and DlCO (-5.28 [95% CI, -9.58 to -0.99] vs. -3.13 [95% CI, -4.35 to -1.92] and -1.32 [95% CI, -2.01 to -0.63]; P < 0.001) than those with medium-term mortality and long-term survival with adjustment for age, sex, and pack-years. Change in FVC in the previous year did not predict FVC change in the subsequent year. CONCLUSIONS: Adults with SSc-ILD have distinct patterns of physiological progression that remain relatively consistent during long-term follow-up; however, recent change in FVC cannot be used to predict future change in FVC within shorter follow-up intervals. The findings of this study provide important information on the course of disease in SSc-ILD and identify specific phenotypes of progression that may improve clinical decision-making and design of future therapeutic trials.

Organizing Pneumonia in an Adult With Chronic Recurrent Noninfectious Osteomyelitis: A Case Report and Literature Review.

Chronic recurrent multifocal osteomyelitis (CRMO) is an idiopathic inflammatory disorder primarily of children and adolescents that is characterized by multifocal nonpyogenic relapsing and remitting inflammatory bone lesions. Pulmonary abnormalities are rarely associated with CRMO, with two reported cases of consolidation on chest CT that occurred in children. We present a case of organizing pneumonia in an adult patient with CRMO. The concurrent worsening of pulmonary and bone disease suggests that CRMO may be a rare cause of organizing pneumonia.

Severity and features of frailty in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by multiple symptoms and comorbidities. The cumulative impact of these deficits can be summarized using the concept of frailty; however, frailty has not been characterized in patients with SSc-ILD. METHODS: Patients with SSc-ILD and non-CTD fibrotic ILD were recruited from specialized clinics. Frailty was assessed using a 42-item patient-reported Frailty Index, calculated as the proportion of reported deficits divided by the total number of surveyed items. Frailty was defined as a Frailty Index >0.21. Unadjusted and multivariate analyses were used to identify correlates of frailty. RESULTS: The study cohort included 86 patients with SSc-ILD and 167 patients with non-CTD fibrotic ILD. The mean age in SSc-ILD was 60.5 years, 80% were women, and on average patients had mild to moderate restrictive lung function impairment (mean FVC 78%-predicted, DLCO 51%-predicted). The mean Frailty Index was 0.23 ± 0.15, with 55% of the SSc-ILD population meeting criteria for frailty. Dyspnea had the strongest association with the Frailty Index (r = 0.62, p < 0.001) and was the only variable independently associated with frailty on multivariate analysis. Frailty severity was similar in SSc-ILD and non-CTD fibrotic ILD, including with adjustment for differences in baseline cohort characteristics. CONCLUSION: Frailty is highly prevalent in patients with SSc-ILD, indicating that chronological age significantly underestimates biological age in this population. Dyspnea is the variable with the strongest association with frailty in SSc-ILD; however, future studies are needed to identify additional modifiable determinants of frailty and the ability of frailty to predict outcomes in SSc-ILD.

Predictors of mortality and progression in scleroderma-associated interstitial lung disease: a systematic review.

BACKGROUND: Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS: Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS: The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS: Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.

Epidemic of lung cancer in patients with HIV infection.

The survival of patients with HIV infection has improved dramatically over the past 20 years, largely owing to a significant reduction in opportunistic infections and AIDs-defining malignancies, such as lymphoma and Kaposi sarcoma. However, with improved survival, patients with HIV are experiencing morbidity and mortality from other (non-AIDs-defining) complications, such as solid organ malignancies. Of these, the leading cause of mortality in the HIV-infected population is lung cancer, accounting for nearly 30% of all cancer deaths and 10% of all non-HIV-related deaths. Importantly, the average age of onset of lung cancer in the HIV-infected population is 25 to 30 years earlier than that in the general population and at lower exposure to cigarette smoke. This article provides an overview of the epidemiology of lung cancer in the HIV-infected population and discusses some of the important risk factors and pathways that may enhance the risk of lung cancer in this population.