Reticulation pattern without honeycombing on high-resolution CT is associated with the risk of disease progression in interstitial lung diseases

Background: The disease course of idiopathic pulmonary fibrosis (IPF) is progressive and occasionally, other types of interstitial lung disease (ILD) may progress similarly to IPF. This study aimed to evaluate risk factors for disease progression within 24 months in patients with various ILDs. Methods: This prospective study obtained 97 patients with a suspected ILD who underwent a transbronchial lung cryobiopsy. The extent of several high-resolution computed tomography (HRCT) patterns was assessed. Due to the inclusion criteria the study population presented a low extent of honeycombing and definite usual interstitial pneumonia (UIP) pattern on HRCT suggesting an early stage of ILD. Disease progression within 24 months despite treatment was defined as a relative decline of ≥ 10% in forced vital capacity (FVC), or a relative decline in FVC of ≥ 5% and one of the three additional criteria: (1) a decline in diffusion capacity to carbon monoxide (DLCO) ≥ 15%; (2) increased fibrosis on HRCT; (3) progressive symptoms, or progressive symptoms and increased fibrosis on HRCT. The same definition was utilized in patients with IPF and other ILDs. Risk factors for disease progression were evaluated in a multivariable logistic regression model. Results: Disease progression was revealed in 52% of the patients with ILD, 51% of the patients with IPF, and 53% of the patients with other types of ILD. A high extent of reticulation on HRCT (Odds ratio [OR] 3.11, 95% Confidence interval [CI] 1.21–7.98, P = 0.019) and never smoking (OR 3.11, CI 1.12–8.63, P = 0.029) were associated with disease progression whereas platelet count (OR 2.06 per 100 units increase, CI 0.96–4.45, P = 0.065) did not quite reach statistical significance. Conclusion: Higher extent of reticulation on HRCT and never smoking appeared to associate with the risk of disease progression within 24 months in ILD patients without honeycombing. Approximately half of the patients with ILD revealed disease progression, and similar proportions were observed in patients with IPF and in other types of ILD.publishedVersionPeer reviewe

A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

WOS:000306840400020Peer reviewe

Are risk predicting models useful for estimating survival of patients with rheumatoid arthritis-associated interstitial lung disease?

Abstract Background: Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients. Methods: Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics

Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis

Abstract Background: Cigarette smoking has been associated with the risk of idiopathic pulmonary fibrosis (IPF). Certain comorbidities have been associated with reduced survival although some studies have indicated that current smokers have a longer survival than ex-smokers. Comorbidities in relation to smoking history have not been previously analyzed. Methods: Retrospective data was collected and patients were categorized according to gender and smoking habits. Comorbidities and medications were collected. Predictive values for mortality were identified by COX proportional hazard analyses. Results: We examined 45 non-smokers (53.3% female), 66 ex-smokers (9.1% female) and 17 current smokers (17.6% female) with IPF. Current smokers were younger at baseline (58.1 ± 8.74 years) compared to non-smokers (71.4 ± 8.74, p < 0.001) and ex-smokers (72.5 ±7.95, p <0.001). Median survival of non-smokers and current smokers was longer (55.0 and 52.0 months, respectively) than that of ex-smokers (36.0 months) (p=0.028 and 0.034, respectively). In age and severity adjusted analyses, smoking was not related to survival. Cardiovascular diseases (CVD) (72.7 %) were the most common comorbidities, current smokers had more chronic obstructive pulmonary disease (COPD) and lung cancer compared to ex-smokers (p<0.001). CVD, COPD and use of insulin were related to poorer survival in adjusted analyses. Conclusions: Smoking seems to influence the course of disease in IPF since current smokers developed the disease at a younger age in comparison to non-smokers and ex-smokers. No significant differences in the major comorbidities were detected between IPF patients with different smoking histories. The mechanism through which smoking influences IPF progression requires further investigation

Comparison of disease progression subgroups in idiopathic pulmonary fibrosis

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia with an unpredictable course. The aims of this study were to retrospectively re-evaluate a cohort of patients with IPF according to the 2011 international IPF guidelines and 1) to characterize the subgroups of patients when classified according to their observed survival times and 2) to evaluate whether Composite Physiologic Index (CPI), Gender-Age-Physiology (GAP) Index or clinical variables could predict mortality. Methods: Retrospective data was collected and patients were classified into subgroups according to their observed lifespans. Differences in clinical variables, CPI and GAP stages as well as in comorbidities were investigated between the subgroups. Predictors of mortality were identified by COX proportional hazard analyses. Results: A total of 132 patients were included in this study. The disease course was rapid (≤ 2 years) in 30.0%, moderate (2—5 years) in 28.0% and slow (≥ 5 years) in 29.0% of the patients. Pulmonary function tests (PFT) and CPI at baseline differentiated significantly between the rapid disease course group and those patients with longer survival times. However, the predictive accuracy of the investigated clinical variables was mainly less than 0.80. The proportions of patients with comorbidities did not differ between the subgroups, but more patients with a rapid disease course were diagnosed with heart failure after the diagnosis of IPF. Most patients with a rapid disease course were categorized in GAP stages I and II, but all patients in GAP stage III had a rapid disease course. The best predictive multivariable model included age, gender and CPI. GAP staging had slightly better accuracy (0.67) than CPI (0.64) in predicting 2-year mortality. Conclusions: Although the patients with a rapid disease course could be differentiated at baseline in terms of PFT and CPI, the predictive accuracy of any single clinical variable as well as CPI and GAP remained low. GAP staging was unable to identify the majority of patients with a rapid disease progression. It is challenging to predict disease progression and mortality in IPF even with risk prediction models

Underlying and immediate causes of death in patients with idiopathic pulmonary fibrosis

Abstract Background: The most common cause of death of patients with idiopathic pulmonary fibrosis (IPF) has been reported to be the lung disease itself and mortality from IPF appears to be increasing. However, the causes of death in patients with IPF taking into account differences between genders and smoking histories as well as disease progression, have not been previously explored. Methods: Retrospective data from hospital register and death certificates from national database of IPF patients treated in Kuopio University Hospital (KUH) from 2002 to 2012 were collected. Mortality was also explored from the death registry database via ICD-10 code J84 revealing the numbers of deaths from pulmonary fibrosis in Finland from 1998 to 2015. Results: Out of 117 deaths, 26.5% were females and 73.5% males in KUH. The most common underlying causes of death were IPF 67.5% and ischemic heart diseases 14.8%. More males died for reasons other than IPF (39.5%) compared to females (12.9%) (p = 0.007). Pneumonia as the immediate cause of death was more common in males (27.9%) than in females (3.2%) (p = 0.004) and in ex-smokers (32.7%) compared to non-smokers (9.3%) (p = 0.007). Death register based mortality from pulmonary fibrosis is increasing in Finland. Conclusions: Even though the overall mortality was higher in males with IPF, the disease-specific mortality for IPF was higher in females i.e. in males, comorbidities were more often the underlying causes of death. Pneumonia-triggered acute exacerbations of IPF may be associated with smoking and gender since females and non-smokers were less likely to succumb to pneumonia. We conclude that disease progression at the end of life may vary depending on smoking habits and gender

Risk factors of clinically significant complications in transbronchial lung cryobiopsy : A prospective multi-center study

Background: The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients. Methods: Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ≤90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications. Results: The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03–1.65, p = 0.027) and young age (OR 7.96, CI 2.32–27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ≤30 days before the TBLC (OR 3.65, CI 0.911–14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10–16.0, p = 0.036). Procedure associated mortality ≤90 days was 1%. Conclusion: The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax.publishedVersionPeer reviewe

Are risk predicting models useful for estimating survival of patients with rheumatoid arthritis-associated interstitial lung disease?

Abstract Background: Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients. Methods: Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics. Results: The median survival was 152 and 61 months in GAP / ILD-GAP stages I and II (p = 0.017). Both GAP and ILD-GAP models accurately estimated 1-year, 2-year and 3-year mortality. CPI (p = 0.025), GAP (p = 0.008) and ILD-GAP (p = 0.028) scores, age (p = 0.002), baseline diffusion capacity to carbon monoxide (DLCO) (p = 0.014) and hospitalization due to respiratory reasons (p = 0.039), were significant predictors of mortality in the univariate analysis, whereas forced vital capacity (FVC) was not predictive. CPI score (HR 1.03, p = 0.018) and baseline DLCO (HR 0.97, p = 0.011) remained significant predictors of mortality after adjusting for age. Conclusions: GAP and ILD-GAP are applicable for evaluating the risk of death of patients with RA-ILD in a similar manner as in those with IPF. Baseline DLCO and CPI score also predicted survival