The Promoter Polymorphism Associates With Severe COVID-19 in the European Population.

Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the promoter polymorphism, rs35705950. The high expressing T-allele is a risk allele for the non-infectious aging lung disease idiopathic pulmonary fibrosis (IPF).

The Extent of Inflammatory Cell Infiltrate and Fibrosis in Lungs of Telomere- and Surfactant-Related Familial Pulmonary Fibrosis.

Familial pulmonary fibrosis (FPF) is a monogenic disease most commonly involving telomere- () or surfactant- () related mutations. These mutations have been shown to alter lymphocytic inflammatory responses, and FPF biopsies with histological lymphocytic infiltrates have been reported. Recently, a model of a surfactant mutation in mice showed that the disease initially started with an inflammatory response followed by fibrogenesis.

Role of Drug-Gene Interactions and Pharmacogenetics in Simvastatin-Associated Pulmonary Toxicity.

Introduction: Simvastatin has previously been associated with drug-induced interstitial lung disease. In this retrospective observational study, cases with non-specific interstitial pneumonia (NSIP) or idiopathic pulmonary fibrosis (IPF) with simvastatin-associated pulmonary toxicity (n = 34) were evaluated.

Objective: To identify whether variations in genes encoding cytochrome P450 (CYP) enzymes or in the SLCO1B1 gene (Solute Carrier Organic anion transporting polypeptide 1B1 gene, encoding the organic anion transporting polypeptide 1B1 [OATP1B1] drug transporter enzyme), and/or characteristics of concomitantly used drugs, predispose patients to simvastatin-associated pulmonary toxicity.

Pulmonary fibrosis in non-mutation carriers of families with short telomere syndrome gene mutations.

Background And Objective: Diagnostic and predictive genetic testing for disease cause and risk estimation is common in many countries. For genetic diseases, predictive test results are commonly straightforward: presence of the mutation involves increased risk for disease and absence of the mutation involves no inherit risk for disease. Germline mutations in telomere-related genes (TRGs) can lead to telomere shortening and are associated with short telomere syndrome (STS).

Pulmonary Sarcoidosis: Diagnosis and Differential Diagnosis.

Sarcoidosis is a multisystem disorder of unknown origin and poorly understood pathogenesis that predominantly affects lungs and intrathoracic lymph nodes and is characterized by the presence of noncaseating granulomatous inflammation in involved organs. The disease is highly heterogeneous and can mimic a plethora of other disorders, making diagnosis a challenge even for experienced physicians. The evolution and severity of sarcoidosis are highly variable: many patients are asymptomatic and their disease course is generally benign with spontaneous resolution.

Patient reported side-effects of prednisone and methotrexate in a real-world sarcoidosis population.

Currently prednisone is the first-line pharmacological treatment option for pulmonary sarcoidosis. Methotrexate is used as second-line therapy and seems to have fewer side-effects. No prospective comparative studies of first-line treatment with methotrexate exist.

Predictors for progressive fibrosis in patients with connective tissue disease associated interstitial lung diseases.

Background: Connective tissue disease associated interstitial lung disease (CTD-ILD) is associated with decreased quality of life and high mortality risk. Outcome and treatment response is unpredictable. This study aimed to identify clinical predictors for CTD-ILD with poor outcome.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression.

Background: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD.

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.

Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests.

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.

Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood.

Health-Related Quality of Life (HRQoL) in Sarcoidosis: Diagnosis, Management, and Health Outcomes.

Health-related quality of life (HRQoL), though rarely considered as a primary endpoint in clinical trials, may be the single outcome reflective of patient priorities when living with a health condition. HRQoL is a multi-dimensional concept that reflects the degree to which a health condition interferes with participation in and fulfillment of important life areas. HRQoL is intended to capture the composite degree of physical, physiologic, psychological, and social impairment resulting from symptom burden, patient-perceived disease severity, and treatment side effects.

Increased Efficacy of Whole Lung Lavage Treatment in Alveolar Proteinosis Using a New Modified Lavage Technique.

Background: Autoimmune pulmonary alveolar proteinosis is an ultra-rare pulmonary disease. Whole lung lavage (WLL) is considered the gold standard therapy. We report a protocol for a new modified lavage technique (nMLT) in which controlled repetitive manual hyperinflation (MH) and intermittent chest percussion are used to enhance WLL efficacy.

ERS clinical practice guidelines on treatment of sarcoidosis.

Background: The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity.

Telomere shortening and DNA damage in culprit cells of different types of progressive fibrosing interstitial lung disease.

Pulmonary fibrosis is strongly associated with telomere shortening and increased DNA damage. Key cells in the pathogenesis involve alveolar type 2 (AT2) cells, club cells and myofibroblasts; however, to what extent these cells are affected by telomere shortening and DNA damage is not yet known. We sought to determine the degree of, and correlation between, telomere shortening and DNA damage in different cell types involved in the pathogenesis of progressive fibrosing interstitial lung disease.

Severe pulmonary toxicity associated with inhalation of pyrethroid-based domestic insecticides (Bop/Sapolio): a case series and literature review.

Purpose Of Review: The current review focuses on serious pulmonary toxicity after inhalation of over the counter available pyrethroid-based insecticides. Pyrethroid is a synthetic product of pyrethrin, which in turn is the active ingredient of pyrethrum, a flower extract.

Recent Findings: On the contrary, a large gap of knowledge exists in the association of interstitial lung disease (ILD) with pyrethroids.

Pulmonary toxicity associated with occupational and environmental exposure to pesticides and herbicides.

Purpose Of Review: Critical review on the notion that exposure to pesticides and herbicides lead to adverse effects in pulmonary health.

Recent Findings: The lung effects of several chemical classes of pesticides and herbicides is biologically plausible. However, the studies that describe the association between exposure and toxic lung effects have numerous limitations.

Switching to an Infliximab Biosimilar Was Safe and Effective in Dutch Sarcoidosis Patients.

The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the effect of switching from Remicade or Inflectra to Flixabi in patients with severe refractory sarcoidosis. This single center retrospective cohort study was performed at St Antonius Hospital Nieuwegein, The Netherlands.

Risk and outcome of COVID-19 infection in sarcoidosis patients: results of a self-reporting questionnaire.

Background: It has been suggested that sarcoidosis patients, especially those on immunosuppressive medications, are at increased risk for COVID-19 infection and more severe disease.

Methods: A questionnaire was developed in four languages (English, Dutch, Italian, and Spanish). The questionnaire queried whether patients had been infected with COVID-19 and outcome of the infection.

Genetic disorders of the surfactant system: focus on adult disease.

Genes involved in the production of pulmonary surfactant are crucial for the development and maintenance of healthy lungs. Germline mutations in surfactant-related genes cause a spectrum of severe monogenic pulmonary diseases in patients of all ages. The majority of affected patients present at a very young age, however, a considerable portion of patients have adult-onset disease.

Current View of Diagnosing Small Fiber Neuropathy.

Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers or both, resulting in sensory changes, autonomic dysfunction or combined symptoms [7]. As a consequence, the symptoms are potentially numerous and have a large impact on quality of life [8].

Methotrexate in sarcoidosis: hematologic and hepatic toxicity encountered in a large cohort over a six year period.

Background: Methotrexate (MTX) is a second line agent for treatment of sarcoidosis. Its long term safety and efficacy in sarcoidosis remains unclear.

Methods: This was a retrospective review of patients seen at the University of Cincinnati Sarcoidosis Clinic over a six year period.