Mortality In Idiopathic Pulmonary Fibrosis Patients Research Articles

The Prognostic Role of Advanced Lung Cancer Inflammation Index in Patients with Idiopathic Pulmonary Fibrosis

Background: The advanced lung cancer inflammation index (ALI) is an innovative and thorough measure designed to assess both inflammation and nutritional status. It includes parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). This research seeks to evaluate the prognosis of idiopathic pulmonary fibrosis (IPF) patients by integrating both inflammation and nutritional status, distinguishing it from conventional inflammation biomarkers. Methods: This study included 102 patients with IPF. Clinical data were extracted from the patients’ medical records. NLR and ALI scores were calculated based on data collected at the initiation of antifibrotic treatment using the following formulas: Neut/Lym for NLR and albumin × BMI/NLR for ALI. Results: ALI values were assessed across various IPF patient subgroups based on gender–age–physiology (GAP) stages (1, 2, and 3), forced vital capacity (FVC) (median split: <70% vs. ≥70%), diffusing capacity for carbon monoxide (DLCO) (<51% vs. ≥51%), 6-Minute Walk Test (6MWT) (<350 vs. ≥350), and the Charlson comorbidity index (CCI) (≤1 vs. >1). Significant differences in ALI were observed with respect to GAP stages, FVC, DLCO, and 6MWT categories (p = 0.000 for all), but not for CCI categories (p = 0.233). Receiver operating characteristic (ROC) curve analysis revealed that ALI had a sensitivity of 63.6% and a specificity of 98.9% at a threshold of 11.2 (AUC = 0.945, 95% CI 0.892–0.998, p < 0.000). Conclusions: Our findings indicate that ALI levels are significantly associated with disease severity and mortality in IPF patients.

IA-Body Composition CT at T12 in Idiopathic Pulmonary Fibrosis: Diagnosing Sarcopenia and Correlating with Other Morphofunctional Assessment Techniques.

Body composition (BC) techniques, including bioelectrical impedance analysis (BIVA), nutritional ultrasound® (NU), and computed tomography (CT), can detect nutritional diagnoses such as sarcopenia (Sc). Sc in idiopathic pulmonary fibrosis (IPF) is associated with greater severity and lower survival. Our aim was to explore the correlation of BIVA, NU and functional parameters with BC at T12 level CT scans in patients with IPF but also its relationship with degree of Sc, malnutrition and mortality. This bicentric cross-sectional study included 60 IPF patients (85.2% male, 70.9 ± 7.8 years). Morphofunctional assessment (MFA) techniques included BIVA, NU, CT at T12 level (T12-CT), handgrip strength, and timed up and go. CT data were obtained using FocusedON®. Statistical analysis was conducted using JAMOVI version 2.3.22 to determine the cutoff points for Sc in T12-CT and to analyze correlations with other MFA techniques. the cutoff for muscle area in T12-CT was ≤77.44 cm2 (area under the curve (AUC) = 0.734, sensitivity = 41.7%, specificity = 100%). The skeletal muscle index (SMI_T12CT) cutoff was ≤24.5 cm2/m2 (AUC = 0.689, sensitivity = 66.7%, specificity = 66.7%). Low SMI_T12CT exhibited significantly reduced median survival and higher risk of mortality compared to those with normal muscle mass (SMI cut off ≥ 28.8 cm/m2). SMI_T12CT was highly correlated with body cell mass from BIVA (r = 0.681) and rectus femoris cross-sectional area (RF-CSA) from NU (r = 0.599). Cronbach's α for muscle parameters across different MFA techniques and CT was 0.735, confirming their validity for evaluating muscle composition. T12-CT scan is a reliable technique for measuring low muscle mass in patients with IPF, specifically when the L3 vertebrae are not captured. An SMI value of <28.8 is a good predictor of low lean mass and 12-month mortality in IPF patients.

The importance of SII and FIB-4 scores in predicting mortality in idiopathic pulmonary fibrosis patients

IntroductionQuick and simple parameters are needed to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In this way, risky patients will have the opportunity to receive early and effective treatment. In this study, we examined whether the Fibrosis-4 index (FIB-4) and systemic immune inflammation index (SII) are associated with mortality in IPF patients. Materials and methodsThe study was designed retrospectively. 100 patients diagnosed with IPF were included in the study. Variables between living patients and deceased patients were examined. ResultsOut of a total of 100 patients, 67 were divided into the surviving group and 33 into the non-surviving group. In multivariate analysis, high FIB-4 and SII values were significantly associated with an increased risk of death. ConclusionFIB-4 and SII are parameters that can predict mortality in IPF patients. In this way, IPF patients with high mortality risk will be identified earlier and more effective methods will be used in follow-up and treatment.

The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Prevalence and clinical impacts of obstructive sleep apnea in patients with idiopathic pulmonary fibrosis: A single-center, retrospective study.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with chronic, progressive lung fibrosis with a poor prognosis. Recent studies have reported a high prevalence of obstructive sleep apnea (OSA) in IPF patients and an association with poor prognosis. This study aimed to evaluate the prevalence, risk factors, and clinical effects on mortality of OSA in patients with IPF. Clinical data were retrospectively analyzed in 167 patients with IPF at Haeundae-Paik Hospital, Republic of Korea. A type 4 portable device was used to monitor OSA, and an apnea-hypopnea index of 5 events per sleep hour and above was diagnosed as OSA. The mean follow-up period and age were 26.9 months and 71.4 years, respectively, with male predominance. OSA was confirmed in 108 patients (64.7%). Mild OSA was the most common (62.1%). Independent risk factors for OSA in the multivariate logistic regression analysis were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.13, p = 0.007), body weight (OR 1.05, 95% CI 1.02-1.09, p = 0.002), and risk based on the Berlin questionnaire (OR 2.76, 95% CI 1.12-6.80, p = 0.028). Shorter six-minute walk distance (6MWD) (hazard ratio [HR] 1.00, 95% CI: 1.00-1.00, p < 0.001), acute exacerbation (AE) (HR 13.83, 95% CI: 5.71-33.47, p < 0.001), and higher percentage of cumulative time with oxygen saturation below 90% in total sleep time (HR 1.08, 95% CI: 1.02-1.14, p = 0.007) were risk factors for mortality in IPF patients in the Cox regression analysis. Approximately two-thirds of the IPF patients had OSA. Older age, higher body weight, and high risk based on the Berlin questionnaire were independent risk factors for OSA in IPF patients. Shorter 6MWD, experience of AE, and night hypoxemia during sleep were associated with a higher risk of mortality in patients with IPF.

Investigating the role of platelets and platelet-derived transforming growth factor-β in idiopathic pulmonary fibrosis.

Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFβ1, although the role of these cells in IPF is ill-defined. In this study, we investigated whether platelets, and specifically platelet-derived TGFβ1, mediate IPF disease progression. Patients with IPF and non-IPF patients were recruited to determine platelet reactivity, and separate cohorts of patients with IPF were followed for mortality. To study whether platelet-derived TGFβ1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl.PF4-Cre) were used in the well-characterized bleomycin-induced pulmonary fibrosis (PF) animal model. In a discovery cohort, we found significantly higher mortality in patients with IPF who had elevated platelet counts within the normal range. However, our validation cohort did not confirm this observation, despite significantly increased platelets, neutrophils, active TGFβ1, and CCL5, a chemokine produced by inflammatory cells, in the blood, lung, and bronchoalveolar lavage (BAL) of patients with IPF. In vivo, we showed that despite platelets being readily detected within the lungs of bleomycin-treated mice, neither the degree of pulmonary inflammation nor fibrosis was significantly different between TGFβ1fl/fl.PF4-Cre and control mice. Our results demonstrate for the first time that platelet-derived TGFβ1 does not significantly mediate inflammation or fibrosis in a PF animal model. Furthermore, our human studies revealed blood platelet counts do not consistently predict mortality in IPF but other platelet-derived mediators, such as C-C chemokine ligand 5 (CCL5), may promote neutrophil recruitment and human IPF.NEW & NOTEWORTHY Platelets are a rich source of profibrotic TGFβ; however, the role of platelets in idiopathic pulmonary fibrosis (IPF) is unclear. We identified that patients with IPF have significantly more platelets, neutrophils, and active TGFβ in their airways than control patients. Using an animal model of IPF, we demonstrated that platelet-derived TGFβ does not significantly drive lung fibrosis or inflammation. Our findings offer a better understanding of platelets in both human and animal studies of IPF.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis

ObjectivesThe study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF).MethodsIn an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT.ResultsNo significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66–0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22–2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco.ConclusionsAirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value.Clinical relevance statementQuantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree.Key Points• AirQuant generates measures of intersegmental tapering and segmental tortuosity.• Automated airway quantification associates with mortality in IPF independent of established measures of disease severity.• Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.Graphical

Prognostic role of CHA2DS2-VASc score for mortality risk assessment in non-advanced idiopathic pulmonary fibrosis: a preliminary observation.

During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

Filtration-histogram based texture analysis and CALIPER based pattern analysis as quantitative CT techniques in idiopathic pulmonary fibrosis: head-to-head comparison.

To assess the prognostic performance of two quantitative CT (qCT) techniques in idiopathic pulmonary fibrosis (IPF) compared to established clinical measures of disease severity (GAP index). Retrospective analysis of high-resolution CT scans for 59 patients (age 70.5 ± 8.8 years) with two qCT methods. Computer-aided lung informatics for pathology evaluation and ratings based analysis classified the lung parenchyma into six different patterns: normal, ground glass, reticulation, hyperlucent, honeycombing and pulmonary vessels. Filtration histogram-based texture analysis extracted texture features: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPPs), skewness and kurtosis at different spatial scale filters. Univariate Kaplan-Meier survival analysis assessed the different qCT parameters' performance to predict patient outcome and refine the standard GAP staging system. Multivariate cox regression analysis assessed the independence of the significant univariate predictors of patient outcome. The predominant parenchymal lung pattern was reticulation (16.6% ± 13.9), with pulmonary vessel percentage being the most predictive of worse patient outcome (p = 0.009). Higher SD, entropy and MPP, in addition to lower skewness and kurtosis at fine texture scale (SSF2), were the most significant predictors of worse outcome (p < 0.001). Multivariate cox regression analysis demonstrated that SD (SSF2) was the only independent predictor of survival (p < 0.001). Better patient outcome prediction was achieved after adding total vessel percentage and SD (SSF2) to the GAP staging system (p = 0.006). Filtration-histogram texture analysis can be an independent predictor of patient mortality in IPF patients. qCT analysis can help in risk stratifying IPF patients in addition to clinical markers.

Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis.

The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC. We retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively). We included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62-7.56, p<0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p<0.01). The frequency of FVC decline in each term was 16-27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively. Six-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.

Quantitative computed tomography measures of skeletal muscle mass in patients with idiopathic pulmonary fibrosis according to a multidisciplinary discussion diagnosis: A retrospective nationwide study in Japan.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease often accompanied by skeletal muscle wasting. We investigated whether skeletal muscle mass and muscle attenuation on computed tomography (CT) are predictors of mortality in IPF patients, using a nationwide cloud-based database and web-based multidisciplinary discussion (MDD) system. IPF patients diagnosed using MDD from April 2009 to March 2014 were included. We analyzed the cross-sectional area (CSA) of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA), muscle attenuation of the ESM (ESMMA), and PM (PMMA) on single-slice axial CT. Survival probability was assessed using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox proportional hazards models were used to evaluate the relationship among the ESMCSA, PMCSA, ESMMA, PMMA, clinical parameters, and prognosis. A total of 199 IPF patients were enrolled. Seventy-four patients died during the study period and the most frequent cause was acute exacerbation (13.1%). The group with the lowest quartile of ESMCSA had significantly worse survival than other groups (P=0.009). Survival rates of the groups with the lowest quartile of PMCSA, lower ESMMA, and lower PMMA did not differ from those of other groups. According to multivariate analysis, ESMCSA<lower quartile was significantly associated with all-cause mortality (hazards ratio, 1.96; P=0.030), whereas, ESMMA<median, PMCSA<lower quartile, and PMMA<median were not. Low ESMCSA on CT images may be a strong risk factor for all-cause mortality in IPF patients based on MDD diagnosis.

Quantitative CT analysis of honeycombing area predicts mortality in idiopathic pulmonary fibrosis with definite usual interstitial pneumonia pattern: A retrospective cohort study.

BackgroundHoneycombing on high-resolution computed tomography (HRCT) images is a key finding in idiopathic pulmonary fibrosis (IPF). In IPF, honeycombing area determined by quantitative CT analysis is correlated with pulmonary function test findings. We hypothesized that quantitative CT-derived honeycombing area (HA) might predict mortality in patients with IPF.Materials and methodsChest HRCT images of 52 IPF patients with definite usual interstitial pneumonia (UIP) pattern were retrospectively evaluated. Mortality data up to July 31, 2016, were recorded. Using a computer-aided system, HA and percentage of HA (%HA) were measured quantitatively. Predictors of 3-year mortality were evaluated using logistic regression models.ResultsThe median %HA, %predicted forced vital capacity (FVC) and composite physiologic index (CPI) were 3.8%, 83.6%, and 33.6, respectively. According to GAP (gender, age, and physiology) stage, 20, 14, and 5 patients were classified under stages I-II-III, respectively. Percentage of HA was significantly correlated with %FVC, CPI, and GAP stage (all, p < 0.001). In univariate analysis, %HA, %FVC, and CPI were statistically significant predictors of mortality. In multivariate analysis using the stepwise regression method, only %HA (odds ratio [OR], 1.27; p = 0.011) was a significant independent predictors of mortality. Patients with %HA ≥ 4.8% had significantly lower survival rates than those with lesser %HA (median survival time, 1.3 vs 5.0 years; log-rank test; p < 0.001).ConclusionQuantitative CT-derived HA might be an important and independent predictor of mortality in IPF patients with definite UIP pattern.

Supine awake subxiphoid lung resection in a severe obese patient with idiopathic pulmonary fibrosis

Surgical biopsy of idiopathic pulmonary fibrosis (IPF) is still associated with not negligible mortality, especially for acute exacerbation. Nowadays, minimally invasive thoracoscopic surgery under general anesthesia is the gold standard procedure. We report a case of a very high-risk patient because of severe obesity and acute respiratory failure who underwent surgical biopsy. A multidisciplinary approach is mandatory to achieve good results in such fragile patients. Awake thoracoscopic subxiphoid approach could be very effective to reduce morbidity and mortality in IPF patients who needs surgical biopsy. The supine position could be useful in obese patients or in patients with difficult airway management.

Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

PurposeThere is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF.MethodsA total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients.ResultsDuring a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.ConclusionsA high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

Prognostic significance of Glasgow prognostic score in patients with acute exacerbation of idiopathic pulmonary fibrosis.

The Glasgow prognostic score (GPS) reflects the host systemic inflammatory response and is a validated independent prognostic factor in lung cancer. We investigated GPS as a potential predictive factor of clinical outcomes in idiopathic pulmonary fibrosis (IPF) patients with acute exacerbation (AE). This was a retrospective study performed between January 2006 and March 2016 in Bucheon St. Mary's Hospital, The Catholic University of Korea. Overall, 327 admitted IPF patients were registered in the study. Patients with definite pneumonia at the time of admission, those with left-sided heart failure, pulmonary embolism and an identifiable cause of acute lung injury, and those whose albumin or C-reactive protein levels were not measured were excluded. A total of 66 patients hospitalized with IPF-AE were finally included. Median survival was 20.7 days and 29 (43.9%) patients died during hospitalization. The median length of overall survival (OS) was 26.0, 20.0 and 15.0 days for GPS-0, GPS-1 and GPS-2, respectively. There were significant differences in OS between GPS-0 and GPS-2 (P = 0.002). In a multivariate analysis performed using a Cox regression model, eosinopenia (P = 0.007), lower partial pressure of oxygen/fraction of inspired oxygen ratio (P = 0.014), and higher GPS (P = 0.006) were independent predictors of mortality. GPS can be helpful in predicting mortality in IPF patients with AE.

Clinical characteristics and factors associated with mortality in idiopathic pulmonary fibrosis: An experience from a tertiary care center in Pakistan.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) that predominantly affects older adults. IPF has the highest mortality burden of all ILDs. Data on mortality in patients with IPF is limited in developing countries. To identify factors associated with mortality in patients with IPF at a tertiary care center in Pakistan. A retrospective chart review was conducted at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients were assessed for smoking status, clinical onset of disease, pulmonary hypertension, disease severity based on spirometry and hypoxemia. A total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45 (18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more common in non-survivors (56.3% P ≤ .01). Pulmonary hypertension was present in 18.8% of patients. 95.4% of patients who had received pirfenidone treatment were alive at the time of study. On multivariate analysis, pirfenidone treatment (OR 0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58-6.84) were the factors associated with mortality. Smoking, age greater than 60 years and hypoxemia were identified as factors that increased the odds of mortality in IPF patients, whereas pirfenidone was found to lower the odds of mortality.

New abilities in therapy of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is progressive fibrosing lung disease with average survival of 2 to 3 years after the diagnosis. Nintedanib is tyro sine kinase inhibitor targeted to receptors of PDGF, FGF and VEGF growth factors. Use of nintedanib in IPF was approved in many countries on the basis of results of TOMORROW phase 2 clinical trial and two phase 3 INPULSIS replicate studies. Significant reduction in the annual FVC decline was shown under the therapy with nintedanib in the INPULSIS studies. Improvement in time to the first exacerbation and stabilization of quality of life measured by SGRQ scale were obtained in the INPULSIS1 study. In pooled analysis of TOMORROW and INPULSIS study results, nintedanib decreased mortality in IPF patients compared to placebo. FVC decline was not differed between patients with typical and possible IPF (i.e., patients with traction bronchiectasis in HRCT, but without surgical lung biopsy) in the INPULSIS trials. In subgroup analysis in INPULSIS trials, the efficacy of nintedanib was confirmed in all IPF patients independently on age, gender, race, baseline FVC and DLCO, presence of emphy sema, use of antireflux therapy or systemic steroids. Frequency of severe adverse events (AE) did not differed between groups of nintedanib and placebo in the INPULSIS trials. The most frequent AE was diarrhea (60%), mostly mild or moderate, which did not require withdrawal the treat ment. Further investigations are needed to study efficacy of nintedanib in IPF patients with more extended inclusion criteria and other fibrosing interstitial lung diseases, as well as efficacy and safety of combinations of nintedanib and pirfenidone. Ideally, the therapeutic strategy in IPF patients should be individualized according to characteristics of the patient.

Supervised exercise training improves exercise cardiovascular function in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease associated with cardiovascular impairments which compromise exercise tolerance and worsen prognosis. To examine the effect of participating in supervised exercise training (ET) program on cardiovascular function in patients with IPF. A randomized controlled study. Outpatient hospital. Thirty-two IPF patients (68±8 years). An ET group (N.=15) participated in a 12-week twice a week 60-minute supervised exercise program while a control group (N.=17) received usual care. At baseline and after the 12-week intervention all patients underwent resting echocardiography, cardiopulmonary exercise testing and N-terminal pro-brain natriuretic peptide (NT-proBNP) assessments. The ET group significantly improved peak values of exercise cardiovascular indexes while the control group showed a trend of deterioration in the outcomes. The mean difference between the groups (95% CI) for circulatory power was 638 mLO2/kg/min/mmHg (95% CI: 197-1080) (P=0.006), cardiac power output 0.3 W (95% CI: 0.1 to 0.6) (P=0.041), and stroke work 312 mL/beat/mmHg (95% CI: 52-573) (P=0.02). No significant differences between groups were detected in most echocardiography measures and NT-proBNP. Changes in exercise cardiovascular indexes showed significant correlation with improvements in functional capacity, dyspnea and quality of life among ET group. Participation in supervised ET program can improve exercise cardiovascular function in patients with IPF, however resting cardiac evaluations seem to be less sensitive to detect such changes. These findings underscore the utility of supervised ET for cardiovascular enhancement which may also be clinically beneficial in reducing the cardiovascular morbidity and mortality in IPF patients.

Body mass index-percent forced vital capacity-respiratory hospitalization: new staging for idiopathic pulmonary fibrosis patients.

Idiopathic pulmonary fibrosis (IPF) is relentless progressive interstitial lung disease. Evaluating predictor of mortality for IPF patients is crucial. The aim of this study was to evaluate the serial trend of important indicators of prognosis and create a useful staging method for IPF patients. We retrospectively searched medical records, pulmonary function tests (PFTs), and chest high resolution computed tomography (HRCT) scans from January 1, 2008 through June 30, 2015 at our hospital. We also evaluated the same parameters 1-year later. We identified 65 IPF patients. The mean age was 71.9±1.8 years (range, 22-85 years). In terms of PFTs, mean percent predicted forced vital capacity (%FVC) was 69.8±2.7. Baseline mean body mass index (BMI) was 24.3±0.6 kg/mm2. Mean survival was 39.2 months (range, 0.9-158.9 months). Cox proportional hazard ratios (HRs) showed the following to be predictors of mortality in IPF patients: 1-year BMI (HR: 0.899; 95% CI: 0.825-0.979; P=0.021); 1-year %FVC (HR: 0.932; 95% CI: 0.887-0.979; P=0.005) and 1-year respiratory hospitalization (HR: 3.307; 95% CI: 2.149-5.090; P<0.001). On the basis of these date, we created a new staging method for predicting mortality for IPF patients, consisting of delta BMI, delta %FVC and respiratory hospitalization within a year following diagnosis of IPF (BFR staging). We stratified patients into one of three groups according to the composite points. Mean survival of stages 1, 2, and 3 was 77.9 (30.8-158.9), 43.9 (0.9-145.2) and 14.8 (3.5-32) months (P<0.001), respectively. In our cohort of IPF patients, this new staging method, including delta BMI and delta %FVC and respiratory hospitalization within 1-year showed a clear survival difference.

Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50–81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO2 was assessed pre to post 6-min walking test (∆SpO2). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3–71.9), p = 0.027), and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5–365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100–105 min/week were associated with a reduced mortality risk and better survival in IPF.