Assessing the Burden and Prognostic Value of Cough in Idiopathic Pulmonary Fibrosis.
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SUBMITTER: Johnston J
PROVIDER: S-EPMC10502888 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Assessing the Burden and Prognostic Value of Cough in Idiopathic Pulmonary Fibrosis.
Johnston Janet J Rivera-Ortega Pilar P
Annals of the American Thoracic Society 20230901 9
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Project description:Chronic cough is experienced by most patients with idiopathic pulmonary fibrosis (IPF). It is often the first symptom and is associated with reduced quality of life, increased rates of depression and anxiety, more severe physiological impairment, and disease progression. Although not fully understood, recent gains in understanding the pathophysiology of chronic cough in IPF have been made. The pathophysiology is likely multifactorial and includes alterations in mucous production and clearance, architectural distortion, and increased cough reflex sensitivity, suggesting a role for targeted therapies and multidisciplinary treatment. Modifiable comorbidities can also induce cough in patients with IPF. There is a renewed emphasis on measuring cough in IPF, with clinical trials of novel and repurposed therapies for chronic cough emerging in this population. This review provides an update on the clinical characteristics, pathophysiology, and measurement of chronic cough in patients with IPF and summarizes recent developments in non-pharmacological and pharmacological therapies.
| S-EPMC9397801 | biostudies-literature
Project description:Background and objectiveIdiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase-7 (MMP-7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP-7 was predictive of mortality in an independent cohort of IPF patients.MethodsMMP-7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP-7 threshold of 12.1 ng/mL with all-cause mortality or transplant-free survival (TFS) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m-PCMI).ResultsMMP-7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 ± 6.55 ng/mL vs 6.03 ± 2.51 ng/mL, P < 0.001). The plasma MMP-7 threshold of 12.1 ng/mL was significantly associated with both all-cause mortality and TFS (unadjusted Cox proportional hazard ratio (HR) = 25.85 and 15.49, 95% CI: 10.91-61.23 and 5.41-44.34, respectively, P < 0.001). MMP-7 concentrations, split by 12.1 ng/mL, were significantly (P < 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP-7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DLCO ) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (r = 0.32, P = 0.001).ConclusionThis study confirms that MMP-7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.
| S-EPMC5352520 | biostudies-literature
Project description:BackgroundCough remains a persistent symptom in patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). To inform future research, treatment and care models, we conducted the first systematic synthesis of evidence on its associated burden.MethodsA literature search was performed for articles published between January 2010 and October 2023 using databases including Embase, MEDLINE and the Cochrane Library. Studies in patients with IPF and other ILDs reporting cough-related measures were eligible for inclusion. Included studies were categorised based on the types of ILD they examined and their design. Study details, patient characteristics and outcomes were extracted, and the risk of bias was assessed. A narrative synthesis approach was employed to interpret the findings.ResultsSixty-one studies were included: 33 in IPF, 18 in mixed-ILDs, six in connective tissue disease-associated-ILDs and four in sarcoidosis. Across the studies, a range of tools to assess cough and its impact were used. The most frequently used measures of cough were cough severity visual analogue scale (VAS) and objective cough counts, whereas the most frequently used health-related quality of life (HRQoL)/impact measures were the St. George's Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). In IPF, studies consistently reported correlations between various cough and HRQoL measures, including between cough VAS scores and objective cough counts, LCQ scores and SGRQ scores. Similar correlations were observed in studies in other ILDs, but data were more limited. Qualitative studies in both IPF and other ILDs consistently highlighted the significant cough-related burden experienced by patients, including disruption of daily activities, fatigue and social embarrassment. Although there were no studies specifically investigating the economic burden of cough, one study in patients with fibrotic ILD found cough severity was associated with workplace productivity loss.ConclusionsOur study underscores the heterogeneity in assessing cough and its impact in IPF and other ILDs. The findings confirm the negative impact of cough on HRQoL in IPF and suggest a comparable impact in other ILDs. Our synthesis highlights the need for standardised assessment tools, along with dedicated studies, particularly in non-IPF ILDs and on the economic burden of cough.
| S-EPMC11351049 | biostudies-literature
Project description: Not available
| S-EPMC5678896 | biostudies-literature
Project description:Rationale and hypothesisIdiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide.MethodsOne hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation < or = 88% during a baseline 6MWT. For patients with a baseline saturation < or = 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation > 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients.ConclusionThese data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.
| S-EPMC2648064 | biostudies-literature
Project description:Rationale: Cough is a commonly reported symptom in idiopathic pulmonary fibrosis (IPF) that negatively impacts patient-reported quality of life (QoL). However, both the burden of cough at diagnosis and the behavior of cough over time have not been systematically described in patients with IPF. Objectives: By utilizing data prospectively collected as part of the PROFILE study, we sought to assess cough burden and the impact that this has on QoL within a cohort of patients with newly diagnosed IPF. We also reexamined the previously described relationship between cough and mortality and the association of cough with the MUC5B promoter polymorphism. Methods: The PROFILE study is a multicenter, prospective, observational, longitudinal cohort study of incident IPF. Scores on the Leicester Cough Questionnaire (LCQ) were recorded at baseline in 632 subjects and then repeated 6 monthly in a subset (n = 216) of the cohort. Results: The median LCQ score at diagnosis was 16.1 (interquartile range, 6.5). LCQ scores remained stable over the subsequent year in the majority of patients. There was a weak association between LCQ score and baseline lung function, with worse cough-related QoL associated with more severe physiological impairment. Cough scores were not associated with subsequent mortality after correcting for baseline lung function. Furthermore, there was no relationship between LCQ score and MUC5B promoter polymorphism status. Conclusions: The burden of cough in IPF is high. Although cough is weakly associated with disease severity at baseline, cough-specific QoL, as measured by the LCQ, confers no prognostic value. Cough-specific QoL burden remains relatively stable over time and does not associate with MUC5B promoter polymorphism.
| S-EPMC10502892 | biostudies-literature
Project description:BackgroundA polymorphism (rs35705950) in the promoter region of the mucin MUC5B is associated with both familial and sporadic forms of idiopathic pulmonary fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the expression of cough, a frequent disabling symptom seen in subjects with IPF.MethodsWe genotyped 136 subjects with IPF. All living subjects were provided with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed allele effects of the MUC5B polymorphism on the LCQ scores using SAS General Linear Models (GLM) in the patients with IPF.ResultsIn the 68 of the total 136 IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent with prior published studies (31%). We found a significant independent effect of the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is independent of other common causes of cough, including gastroesophogeal reflux disease and upper airway cough syndrome.ConclusionsCough severity, a common disabling phenotypic component of IPF, is significantly associated with the presence of the minor allele of a MUC5B promoter polymorphism. This study highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary fibrosis.
| S-EPMC4038402 | biostudies-literature
Project description:Dyspnea is a hallmark symptom of idiopathic pulmonary fibrosis (IPF), and dyspnea induced physical activity limitation is a prominent driver of quality of life impairment among IPF patients.We examined response data for the 21 physical activity items (the first 21 of 24) from the University of California San Diego Shortness of Breath Questionnaire (UCSD) collected at baseline in a recently conducted IPF trial. We used Rasch analysis and hypothesis testing with conventional statistical methodology to achieve three objectives: 1) to examine the items to identify the one characteristic that distinguishes one from another; 2) to asses these items for their ability to measure dyspnea severity in IPF; 3) to use the items to develop a dyspnea ruler.The sample comprised 178 subjects. The 21 items fit the Rasch model. There was very strong correlation between Rasch item severity and their metabolic equivalents (METS) values (r = -0.86, p < 0.0001). With the sample stratified on scores from the 21 items, there were significant between group differences in FVC%, DLCO% and distance walked during the six-minute walk test. The dyspnea ruler can be used to put dyspnea levels in a more easily understood clinical context.The first 21 items from the UCSD compose a unidimensional dyspnea-with-activity scale and are both sensibly ordered and distinguished from each other by their METS values. These 21 items can be used confidently to formulate clinically-relevant inferences about IPF patients and should be considered for use as a meaningful endpoint in IPF research.
| S-EPMC3951298 | biostudies-literature
Project description:BackgroundTripartite motif (TRIM) family genes get involved in the pathogenesis and development of various biological processes; however, the prognostic value of TRIM genes for idiopathic pulmonary fibrosis (IPF) needs to be explored.MethodsWe acquired gene expression based on bronchoalveolar lavage (BAL) cells and clinical data of three independent IPF cohorts in the GSE70866 dataset from the Gene expression omnibus (GEO) database. Differentially expressed TRIM genes (DETGs) between IPF patients and healthy donors were identified and used to establish a risk signature by univariate and multivariate Cox regression analysis in the training cohort. The risk signature was further validated in other IPF cohorts, and compared with previously published signatures. Moreover, we performed functional enrichment analysis to explore the potential mechanisms. Eventually, the quantitative real time PCR was conducted to validate the expressions of the key genes in BAL from 12 IPF patients and 12 non-IPF controls from our institution.ResultsWe identified 4 DETGs including TRIM7, MEFV, TRIM45 and TRIM47 significantly associated with overall survival (OS) of IPF patients (P < 0.05). A multiple stepwise Cox regression analysis was performed to construct a 4-TRIM-gene prognostic signature. We categorized IPF patients into one low-risk group and the other high-risk group as per the average risk value of the TRIM prognostic signature in the training and validation cohorts. The IPF individuals in the low-risk group demonstrated an obvious OS advantage compared with the high-risk one (P < 0.01). The time-dependent receiver operating characteristic approach facilitated the verification of the predictive value of the TRIM prognostic signature in the training and validation cohorts, compared with other published signatures. A further investigation of immune cells and IPF survival displayed that higher proportion of resting memory CD4+ T cells and resting mast cells harbored OS advantage over lower proportion, however lower proportion of neutrophils, activated dendritic cells and activated NK cells indicated worse prognosis.ConclusionThe TRIM family genes are significant for the prognosis of IPF and our signature could serve as a robust model to predict OS.
| S-EPMC9724366 | biostudies-literature
Project description:No studies on idiopathic pulmonary fibrosis (IPF) have investigated the prognostic impact of extrapulmonary cancers in patients with IPF. We aimed to determine the prognostic impact of malignancies in patients with IPF. We retrospectively reviewed the medical records of patients diagnosed with IPF between 2001 and 2015. Patients were divided into three groups: IPF without cancer (n = 440), IPF with lung cancer (n = 69), and IPF with extrapulmonary cancer (n = 70). Of the 579 patients with IPF, 139 (24%) had cancer; the three most common types were lung (11.9%), gastric (2.4%), and colorectal (1.9%). Survival was significantly worse in patients with lung cancer than in those without cancer (hazard ratio [HR] = 1.83, 95% confidence interval [CI], 1.35-2.48) or those with extrapulmonary cancer (HR = 1.70, 95% CI, 1.14-2.54). The rate of hospitalisation for cancer-related complications was significantly higher in IPF patients with lung cancer than in those with extrapulmonary cancer. The annual rates of decline in percent predicted forced vital capacity and diffusion capacity for carbon monoxide did not differ among the groups. Physicians should pay attention to the development and progression of cancer and its prognostic impact in patients with IPF.
| S-EPMC7588444 | biostudies-literature