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An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

ABSTRACT: Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.

SUBMITTER: Caminati A

PROVIDER: S-EPMC9487338 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

Caminati Antonella A Cavazza Alberto A Sverzellati Nicola N Harari Sergio S

European respiratory review : an official journal of the European Respiratory Society 20120901 125

Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic ...[more]

PMID: 22941885

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Project description:BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of other forms of ILD and a compatible surgical lung biopsy. Bronchoalveolar lavage (BAL) is commonly proposed for the diagnosis of ILD, including PLCH, but the diagnostic value of this technique is limited. Here, we have analyzed the levels of a panel of cytokines and chemokines in BAL from PLCH patients, in order to identify a distinct immune profile to discriminate PLCH from other smoking related-ILD (SR-ILD), and comparing the results with idiopathic pulmonary fibrosis (IPF) as another disease in which smoking is considered a risk factor.MethodsBAL samples were collected from thirty-six patients with different ILD, including seven patients with PLCH, sixteen with SR-ILD and thirteen with IPF. Inflammatory profiles were analyzed using the Human Cytokine Membrane Antibody Array. Principal component analysis (PCA) was performed to reduce dimensionality and protein-protein interaction (PPI) network analysis using STRING 11.5 database were conducted. Finally, Random forest (RF) method was used to build a prediction model.ResultsWe have found significant differences (p < 0.05) on thirty-two cytokines/chemokines when comparing BAL from PLCH patients with at least one of the other ILD. Four main groups of similarly regulated cytokines were established, identifying distinct sets of markers for each cluster. Exploratory analysis using PCA (principal component analysis) showed clustering and separation of patients, with the two first components capturing 69.69% of the total variance. Levels of TARC/CCL17, leptin, oncostatin M (OSM) and IP-10/CXCL10 were associated with lung function parameters, showing positive correlation with FVC. Finally, random forest (RF) algorithm demonstrates that PLCH patients can be differentiated from the other ILDs based solely on inflammatory profile (accuracy 96.25%).ConclusionsOur results show that patients with PLCH exhibit a distinct BAL immune profile to SR-ILD and IPF. PCA analysis and RF model identify a specific immune profile useful for discriminating PLCH.

Project description:Interstitial lung diseases (ILDs) are a diverse group of ∼200 acute and chronic pulmonary disorders that are characterized by variable amounts of inflammation, fibrosis and architectural distortion with substantial morbidity and mortality. Inaccurate and delayed diagnoses increase the risk, especially in developing countries. Studies have indicated the significant roles of genetic elements in ILDs pathogenesis. Therefore, the first genetic knowledge resource, ILDgenDB, has been developed with an objective to provide ILDs genetic data and their integrated analyses for the better understanding of disease pathogenesis and identification of diagnostics-based biomarkers. This resource contains literature-curated disease candidate genes (DCGs) enriched with various regulatory elements that have been generated using an integrated bioinformatics workflow of databases searches, literature-mining and DCGs-microRNA (miRNAs)-single nucleotide polymorphisms (SNPs) association analyses. To provide statistical significance to disease-gene association, ILD-specificity index and hypergeomatric test scores were also incorporated. Association analyses of miRNAs, SNPs and pathways responsible for the pathogenesis of different sub-classes of ILDs were also incorporated. Manually verified 299 DCGs and their significant associations with 1932 SNPs, 2966 miRNAs and 9170 miR-polymorphisms were also provided. Furthermore, 216 literature-mined and proposed biomarkers were identified. The ILDgenDB resource provides user-friendly browsing and extensive query-based information retrieval systems. Additionally, this resource also facilitates graphical view of predicted DCGs-SNPs/miRNAs and literature associated DCGs-ILDs interactions for each ILD to facilitate efficient data interpretation. Outcomes of analyses suggested the significant involvement of immune system and defense mechanisms in ILDs pathogenesis. This resource may potentially facilitate genetic-based disease monitoring and diagnosis.Database URL: http://14.139.240.55/ildgendb/index.php.

Project description:BackgroundCigarette smoking is a risk factor for interstitial lung abnormalities (ILAs) and interstitial lung diseases (ILDs). Investigation defining the relationships between ILAs/ILDs and clinical, radiographic, and pathologic findings in smokers have been incomplete. Employing a cohort undergoing surgical resection for lung nodules/masses, we (1) define the prevalence of ILAs/ILDs, (2) delineate their clinical, radiographic and pathologic predictors, and (3) determine their associations with mortality.MethodsPatients undergoing resection of lung nodules/masses between 2017 and 2020 at a rural Appalachian, tertiary medical center were retrospectively investigated. Predictors for ILAs/ILDs and mortality were assessed using multivariate logistic regression analysis.ResultsIn the total study cohort of 352 patients, radiographic ILAs and ILDs were observed in 35.2% and 17.6%, respectively. Among ILA patterns, subpleural reticular changes (14.8%), non-emphysematous cysts, centrilobular (CL) ground glass opacities (GGOs) (8% each), and mixed CL-GGO and subpleural reticular changes (7.4%) were common. ILD patterns included combined pulmonary fibrosis emphysema (CPFE) (3.1%), respiratory bronchiolitis (RB)-ILD (3.1%), organizing pneumonitis (2.8%) and unclassifiable (4.8%). The group with radiographic ILAs/ILDs had a significantly higher proportion of ever smokers (49% vs. 39.9%), pack years of smoking (44.57 ± 36.21 vs. 34.96 ± 26.22), clinical comorbidities of COPD (35% vs. 26.5%) and mildly reduced diffusion capacity (% predicated 66.29 ± 20.55 vs. 71.84 ± 23). Radiographic centrilobular and paraseptal emphysema (40% vs. 22.2% and 17.6% vs. 9.6%, respectively) and isolated traction bronchiectasis (10.2% vs. 4.2%) were associated with ILAs/ILDs. Pathological variables of emphysema (34.9% vs. 18.5%), any fibrosis (15.9% vs. 4.6%), peribronchiolar metaplasia (PBM, 8% vs. 1.1%), RB (10.3% vs. 2.5%), and anthracosis (21.6% vs. 14.5%) were associated with ILAs/ILDs. Histologic emphysema showed positive correlations with any fibrosis, RB, anthracosis and ≥ 30 pack year of smoking. The group with ILAs/ILDs had significantly higher mortality (9.1% vs. 2.2%, OR 4.13, [95% CI of 1.84-9.25]).ConclusionsIn a rural cohort undergoing surgical resection, radiographic subclinical ILAs/ILDs patterns were highly prevalent and associated with ever smoking and intensity of smoking. The presence of radiographic ILA/ILD patterns and isolated honeycomb changes were associated with increased mortality. Subclinical ILAs/ILDs and histologic fibrosis correlated with clinical COPD as well as radiographic and pathologic emphysema emphasizing the co-existence of these pulmonary injuries in a heavily smoking population.

Project description:BackgroundThe R-Scale-PF was proposed to evaluate the health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF). We generated a German version of the R-Scale-PF (GR-Scale), representing the first translation of the questionnaire into another language and assessed HRQoL longitudinally in various interstitial lung diseases (ILDs) using the R-Scale-PF scoring system at a specialized ILD centre.MethodsWe have translated the questionnaire in accordance with the WHO translation guidelines and applied it to 80 ILD patients of our department, with follow-ups after 3-6 months, assessing its internal consistency, floor and ceiling effects, concurrent validity, known-groups validity, and its responsiveness to changes over time.ResultsAt baseline, all 80 patients completed the GR-Scale. In 70 patients (87.5%), follow-up data could be obtained after 4.43 ± 1.2 months. The GR-Scale demonstrated acceptable internal consistency (Cronbach's α 0.749) and slight floor effects. Concurrent validity analysis showed weak but significant correlations with forced vital capacity (FVC; r=-0.282 p = 0.011) and diffusion capacity for carbon monoxide (DLco; r=-0.254 p = 0.025). In the follow-up analysis, moderate correlations were found with FVC (r=-0.41 p < 0.001) and DLco (r=-0.445 p < 0.001). No significant difference in the total score was found between patients with IPF (n = 10) and with non-IPF ILDs (n = 70). The GR-Scale successfully discriminated between groups of varying disease severity based on lung function parameters and the need for long-term oxygen therapy (LTOT). Furthermore, it was able to distinguish between patients showing improvement, stability or decline of lung function parameters.ConclusionOur prospective observational pilot study suggests that the GR-Scales is a simple and quick tool to measure HRQoL in patients with ILDs, thus providing an important additional information for the clinical assessment of ILD patients.Trial registrationOur study was retrospectively registered in the German Clinical Trial Register (DRKS) on 02.11.2022 (DRKS-ID: DRKS00030599).

Dataset Information

An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

Publications

An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

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