Mixed Ventilatory Defects in Pulmonary Sarcoidosis

Kouranos, Vasileios; Ward, Simon; Kokosi, Maria; Castillo, Diego; Chua, Felix; Judge, Eoin P.; Thomas, Suzie; Tonder, Frans van; Devaraj, A.; Nicholson, Andrew G.; Maher, Toby M.; Renzoni, Elisabetta; Wells, Adrian

doi:10.1016/j.chest.2020.04.074

Cited by 32 publications

(20 citation statements)

References 17 publications

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“…In general, lung diseases fall into two categories: 1) restrictive diseases, which include a reduction in the ability of the lungs to expand and 2) obstructive diseases, which cause increased airway resistance and restricted airflow. Restrictive or obstructive diseases a classified based on clinical measures, including the ratio of forced expiratory volume to full forced lung capacity in one second (FEV1/FVC) and total lung capacity percentage (TLC %) (Kouranos et al, 2020). The restrictive disease is characterized by a decrease in the TLC% with no change or increase in the FEV1/FVC ratio because either both indicators decrease simultaneously or forced expiratory volume in one second (FEV1) increases with decreased lung compliance.…”

Section: Pathological Changes Of Lungmentioning

confidence: 99%

An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

Gong

Yang

Wen³

et al. 2021

Front. Cell Dev. Biol.

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Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.

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Section: Pathological Changes Of Lungmentioning

confidence: 99%

An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

Gong

Yang

Wen³

et al. 2021

Front. Cell Dev. Biol.

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“…VIF values 5.85 and 4.42 for FVC and FeV1 respectively can be easily anticipated by the fact that in restrictive lung diseases FeV1 depends on FVC. However, the importance of FeV1 for LUNG and GHS score is an interesting observation in regard of a recent description of different ventilatory defects in a large cohort of sarcoidosis patients [ 27 ]; an obstructive ventilator defect was found in approximately 15% of patients in our cohort. Especially in obstructive and mixed ventilatory defects, FeV1 may better reflect airway involvement and thereby explain reduced quality of life.…”

Section: Discussionmentioning

confidence: 64%

FeV1 and BMI influence King’s Sarcoidosis Questionnaire score in sarcoidosis patients

et al. 2021

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Background Sarcoidosis is granulomatous disease of unknown origin affecting organ function and quality of life. The King’s Sarcoidosis Questionnaire (KSQ) serves as a tool to assess quality of life in sarcoidosis patients with general health and organ specific domains. A German translation has been validated in a German cohort. In this study we assessed, whether clinical parameters influence KSQ scores. Methods Clinical data (e.g. lung function, organ impairment, serological parameters) for the German validation cohort were extracted from clinical charts and investigated by correlation and linear regression analyses. Results KSQ subdomain scores were generally lower in patients with respective organ manifestation or on current therapy. LUNG subdomain was significantly predicted by lung functional parameters, however for general health status, only FeV1 exerted significant influence. GHS was not influenced by serological parameters, but was significantly negatively correlated with body mass index (BMI). KSQ provides additional information beyond lung function, clinical or serological parameters in sarcoidosis patients. Notably, high BMI is significantly negatively associated with patients’ well-being as measured by KSQ-GHS. Conclusion This observation may direct further studies investigating the effect of obesity on sarcoidosis-related quality of life and strategies to intervene with steroid-sparing therapies and measures of life style modifications. Trial registration This study was registered in the German Clinical Trials Register (reference number DRKS00010072). Registered January 2016.

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“…Identifying and validating outcome measures is one of the greatest tasks at hand in organ-specific or multi-organ trial design in sarcoidosis. Even when considering a prevalent manifestation such as pulmonary sarcoidosis, the most used measures such as FVC can be flawed in capturing clinically meaningful change ( 126 ); and may miss a large subset of patients with ventilatory defects affecting other PFT parameters ( 127 ). Another example is though improvement in HRQoL along with the minimum clinically important difference (MCID) for various HRQoL instruments has been reported with some treatment regimens ( 128 , 129 ), correlative changes in HRQoL to other endpoints such as physiologic function or steroid-tapering are still lacking.…”

Section: Challenges Affecting Drug Trials and Drug Development In Sar...mentioning

confidence: 99%

Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches

et al. 2022

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Sarcoidosis is a systemic granulomatous inflammatory disease of unknown etiology. It affects the lungs in over 90% of patients yet extra-pulmonary and multi-organ involvement is common. Spontaneous remission of disease occurs commonly, nonetheless, over 50% of patients will require treatment and up to 30% of patients will develop a chronic progressive non-remitting disease with marked pulmonary fibrosis leading to significant morbidity and death. Guidelines outlining an immunosuppressive treatment approach to sarcoidosis were recently published, however, the strength of evidence behind many of the guideline recommended drugs is weak. None of the drugs currently used for the treatment of sarcoidosis have been rigorously studied and prescription of these drugs is often based on off-label” indications informed by experience with other diseases. Indeed, only two medications [prednisone and repository corticotropin (RCI) injection] currently used in the treatment of sarcoidosis are approved by the United States Food and Drug Administration. This situation results in significant reimbursement challenges especially for the more advanced (and often more effective) drugs that are favored for severe and refractory forms of disease causing an over-reliance on corticosteroids known to be associated with significant dose and duration dependent toxicities. This past decade has seen a renewed interest in developing new drugs and exploring novel therapeutic pathways for the treatment of sarcoidosis. Several of these trials are active randomized controlled trials (RCTs) designed to recruit relatively large numbers of patients with a goal to determine the safety, efficacy, and tolerability of these new molecules and therapeutic approaches. While it is an exciting time, it is also necessary to exercise caution. Resources including research dollars and most importantly, patient populations available for trials are limited and thus necessitate that several of the challenges facing drug trials and drug development in sarcoidosis are addressed. This will ensure that currently available resources are judiciously utilized. Our paper reviews the ongoing and anticipated drug trials in sarcoidosis and addresses the challenges facing these and future trials. We also review several recently completed trials and draw lessons that should be applied in future.

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Mixed Ventilatory Defects in Pulmonary Sarcoidosis

Cited by 32 publications

References 17 publications

An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

FeV1 and BMI influence King’s Sarcoidosis Questionnaire score in sarcoidosis patients

Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches

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