Long COVID syndrome and the lung: how long will it last?

The prevalence and duration of the long-term respiratory complications of COVID-19 infection remains to be elucidated. This short commentary reports on recently published studies in patients post-acute COVID-19 infection in terms of symptom prevalence, physiological and radiological sequela and where only symptoms are present despite investigation. Pulmonary function testing, 6-min walk tests, computed tomography chest and more advanced imaging modalities have been incorporated to reveal the underlying pathophysiology that cause such disabling symptoms in patient with post-acute COVID-9 syndrome (PACS). PACS has a serious impact on people's ability to return to work, affecting the physical, mental, social sphere and with significant healthcare and general economic consequences for them, their families and society.

Lung organoids and other preclinical models of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease affecting over 100 000 people in Europe with an increasing incidence. Available treatments offer only slowing of disease progression and are poorly tolerated by patients leading to cessation of therapy. Lung transplant remains the only cure. Therefore, alternative treatments are urgently required. The pathology of IPF is complex and poorly understood and thus creates a major obstacle to the discovery of novel treatments. Additionally, preclinical assessment of new treatments currently relies upon animal models where disparities with human lung biology often hamper drug development. At a cellular level, IPF is characterized by persistent and abnormal deposition of extracellular matrix by fibroblasts and alveolar epithelial cell injury which is seen as a key event in initiation of disease progression. In-depth investigation of the role of alveolar epithelial cells in health and disease has been impeded due to difficulties in primary cell isolation and culture ex vivo. Novel strategies employing patient-derived induced pluripotent stem cells engineered to produce type 2 alveolar epithelial cells (iAEC2) cultured as three-dimensional organoids have the potential to overcome these hurdles and inform new effective precision treatments for IPF leading to improved survival and quality of life for patients worldwide.

Exploring the barriers and facilitators for the use of digital health technologies for the management of COPD: a qualitative study of clinician perceptions.

BACKGROUND: Digital health technology (DHT) promises to support patients and healthcare professionals (HCPs) to optimize the management of chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence demonstrating the effectiveness of DHT for the management of COPD. One reason for this is the lack of user-involvement in the development of DHT interventions in COPD meaning their needs and preferences are rarely accounted for in the design phase. Although HCP adoption issues have been identified in relation to DHT, little is known about the challenges perceived by HCPs providing care to COPD patients. Therefore, this study aims to qualitatively explore the barriers and facilitators HCPs perceive for the use of DHT in the management of COPD. METHODS: Participants (n = 32) were recruited using snowball sampling from two university hospitals and several general practitioner clinics. A semi-structured interview was conducted with each participant. NVivo 12 software was used to complete thematic analysis on the data. RESULTS: Themes identified include: data quality; evidence-based care; resource constraints; and digital literacy presented as barriers; and facilitators include the following themes: digital health training and education; improving HCP digital literacy; and Personalized prescribing. Patient-centered approaches, such as pulmonary rehabilitation and shared decision-making were suggested as implementation strategies to ease the adoption of digital health for the management of COPD. CONCLUSION: These findings contribute new insights about the needs and preferences of HCPs working in COPD regarding DHT. The findings can be used to help mitigate user-experience issues by informing the design of person-centered implementation and adoption strategies for future digital health interventions in COPD.

Toll-like receptor 3 L412F polymorphism promotes a persistent clinical phenotype in pulmonary sarcoidosis.

BACKGROUND/INTRODUCTION: Sarcoidosis is a multi-systemic disorder of unknown etiology, characterized by the presence of non-caseating granulomas in target organs. In 90% of cases, there is thoracic involvement. Fifty to seventy percent of pulmonary sarcoidosis patients will experience acute, self-limiting disease. For the subgroup of patients who develop persistent disease, no targeted therapy is currently available. AIM: To investigate the potential of the single nucleotide polymorphism (SNP), Toll-like receptor 3 Leu412Phe (TLR3 L412F; rs3775291), as a causative factor in the development of and in disease persistence in pulmonary sarcoidosis. To investigate the functionality of TLR3 L412F in vitro in primary human lung fibroblasts from pulmonary sarcoidosis patients. DESIGN: SNP-genotyping and cellular assays, respectively, were used to investigate the role of TLR3 L412F in the development of persistent pulmonary sarcoidosis. METHODS: Cohorts of Irish sarcoidosis patients (n = 228), healthy Irish controls (n = 263) and a secondary cohort of American sarcoidosis patients (n = 123) were genotyped for TLR3 L412F. Additionally, the effect of TLR3 L412F in primary lung fibroblasts from pulmonary sarcoidosis patients was quantitated following TLR3 activation in the context of cytokine and type I interferon production, TLR3 expression and apoptotic- and fibroproliferative-responses. RESULTS: We report a significant association between TLR3 L412F and persistent clinical disease in two cohorts of Irish and American Caucasians with pulmonary sarcoidosis. Furthermore, activation of TLR3 in primary lung fibroblasts from 412 F-homozygous pulmonary sarcoidosis patients resulted in reduced IFN-ß and TLR3 expression, reduced apoptosis- and dysregulated fibroproliferative-responses compared with TLR3 wild-type patients. DISCUSSION/CONCLUSION: This study identifies defective TLR3 function as a previously unidentified factor in persistent clinical disease in pulmonary sarcoidosis and reveals TLR3 L412F as a candidate biomarker.

The lady with the dragon tattoo.

BACKGROUND: Though the skin is affected in sarcoidosis in about one-third of cases, granulomatous tattoo reactions are an unusual manifestation of the disease. It is important phenomenon to recognize, as it frequently leads to the diagnosis of systemic sarcoidosis. CASE PRESENTATION: A 35-year-old Caucasian female with multiple tattoos presented with a 5-week history of tenderness of the black dye in a tattoo depicting a dragon. She also described a 15-month history of fatigue, polyarthralgia, and mild dyspnea. Skin biopsy demonstrated multiple dermal non-caseating granulomata with associated tattoo ink. Further investigation revealed the presence of systemic sarcoidosis. Her symptoms and skin changes improved with conservative management. CONCLUSION: Sarcoidal tattoo reactions in those without systemic sarcoidosis are a rare occurrence, and their presence should prompt a search for systemic involvement. The accurate identification of skin involvement in sarcoidosis is important, as it tends to occur early in the course of disease, and the skin is a readily accessible site for biopsy, allowing for prompt diagnosis.

Adalimumab for refractory pulmonary sarcoidosis.

BACKGROUND: Ireland has one of the highest prevalence of sarcoidosis globally. Currently anti-TNF treatment in sarcoidosis is considered on a case-by-case basis particularly in patients who have a sub-optimal response to corticosteroid therapy. AIMS: We report our experience of Adalimumab in a series of refractory pulmonary sarcoidosis and discuss implications for treatment. CONCLUSION: Symptomatic improvement was found in all patients as well as stabilisation or improvement in DLCO sb. Improvements in pulmonary function tests correlated well to radiological stage and length of disease.