December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

No abstract available. Article truncated after 150 words. History of Present Illness A 56-year-old man was referred for a second opinion on recent onset of diffuse parenchymal lung disease. He had started noting mild dyspnea with yard work approximately in March 2021. His symptoms progressed over the next month with increasing shortness of breath and some fever. He presented to outside emergency department on April 17, 2021 and chest CT showing patchy ground-glass opacities with some areas of irregular consolidation (Figure 1). He was subsequently seen by an outside pulmonologist and started empirically on prednisone (50 mg/day). An outside lung biopsy had been performed which showed nonspecific interstitial pneumonitis. There was some improvement in his symptoms and his prednisone dose was reduced to 20 mg/day; however, his symptoms subsequently worsened with saturations noted to drop to 85% with any ambulation. He also had swelling of his left face and a biopsy of the parotid gland with the findings …

Autophagy in Cancer Therapy—Molecular Mechanisms and Current Clinical Advances

Autophagy is a crucial general survival tactic of mammalian cells. It describes the capability of cells to disassemble and partially recycle cellular components (e.g., mitochondria) in case they are damaged and pose a risk to cell survival or simply if their resources are urgently needed elsewhere at the time. Autophagy-associated pathomechanisms have been increasingly recognized as important disease mechanisms in non-malignant (neurodegeneration, diffuse parenchymal lung disease) and malignant conditions alike. However, the overall consequences of autophagy for the organism depend particularly on the greater context in which autophagy occurs, such as the cell type or whether the cell is proliferating. In cancer, autophagy sustains cancer cell survival under challenging, i.e., resource-depleted, conditions. However, this leads to situations in which cancer cells are completely dependent on autophagy. Accordingly, autophagy represents a promising yet complex target in cancer treatment with therapeutically induced increase and decrease of autophagic flux as important therapeutic principles.

Risk Factors Associated With Mortality in Hypersensitivity Pneumonitis: A Meta-analysis

Purpose: Hypersensitivity pneumonitis (HP), an immune-mediated form of diffuse parenchymal lung disease (DPLD), is triggered by inhalation of a wide variety of allergens in susceptible individuals. Several studies suggest that the death rate associated with this disease has increased significantly in recent years. This meta-analysis investigates the significant clinico-radiological characteristics which may be appraised as potential risk factors associated with disease mortality.Methods: Extensive literature search was conducted for original articles published between January 2009 and April 2021 through PubMed, Google Scholar, EMBASE, and Cochrane Library using the keywords: “hypersensitivity pneumonitis”, “hazard ratio” and “mortality”. Results: A total of 21 independent studies related to mortality of HP subjects could be identified. The combined results of univariate and multivariate analysis suggest that older age [univariate odds ratio (OR) 1.038 (1.028-1.048); multivariate OR 1.036, (1.025-1.046)], male subjects [univariate OR 1.508, (1.240- 1.834); multivariate OR 1.396, (1.004-1.943)], honeycombing [univariate OR 1.086 (1.065- 1.108); multivariate OR 1.121 (1.070- 1.175)] and traction bronchiectasis [univariate OR 1.141 (1.092- 1.192); multivariate OR 1.107 (1.048-1.169)] are significantly associated with mortality risk of HP subjects. Further, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), ground glass opacity (GGO) and mosaic attenuation were associated with lower risk of all-cause mortality. Although smoking status correlated with mortality risk in these patients, the findings appeared to be insignificant. Conclusion: Individual male subjects with older age and presence of extensive fibrosis, i.e., honeycombing and traction bronchiectasis experience an increased mortality risk.

Outcome of ventilation in patients with hypercapnic respiratory failure in IPF patients: A prospective study

Background: Diffuse parenchymal lung disease (DPLD) is the inflammation and fibrosis of lung interstitium, resulting in respiratory failure. The rate of hypoxic respiratory failure is high as the disease progresses. In idiopathic pulmonary fibrosis (IPF) patients, acute deterioration leads to type 2 respiratory failure, etiology and management of which remains to be completely understood. Aims and Objectives: To identify the causes of type 2 respiratory failure and assess the outcome of invasive and non-invasive ventilation in patients with IPF. Materials and Methods: This prospective single center study included >18-year-old 44 patients with IPF. History of patients, complete blood count, chest radiograph, urine routine, spirometry with bronchodilator reversibility, DLCO (diffusing capacity for carbon monoxide) testing, arterial blood gas measurements, and antinuclear antibody (ANA) test were evaluated. Results: Fourteen (31.8%) patients developed type 2 respiratory failure (within 1.5–6 years from the time of onset of illness). Causes of respiratory failure included acute exacerbation of IPF (35.71%), infections (14.29%), heart failure (14.29%), ischemic heart disease (14.29%), pulmonary embolism (21.43%), pneumothorax (7.14%), and surgical lung biopsy (7.14%). Patients were initiated on non-invasive mechanical ventilation (NIV) (64.29%) and invasive mechanical ventilation (IMV) (35.71%). Eight (88.89%) out of 9 patients on NIV survived, whereas all 5 patients (100%) on IMV expired. Conclusion: Considering the higher mortality rate associated with IMV, NIV is a better technique than IMV for improving patient outcome and management. NIV may be effectively implemented for improving the treatment outcome in patients with IPF and avoiding any aggressive therapeutic approaches.

A Rare Case Diagnosed by Videothoracoscopic Lung Biopsy: Diffuse Pulmonary Meningotheliomatosis

Diffuse pulmonary meningotheliomatosis (DPM) is reported as a diffuse parenchymal lung disease characterized by disseminating small asymptomatic nodules. These lesions are often detected incidentally as microscopic findings in lung specimens or autopsies examined by a pathologist. We report a case of a 60-year-old male asymptomatic patient presenting with multiple bilateral pulmonary nodules on high-resolution computed tomography and diagnosed by videothoracoscopic surgery. Differential diagnosis of patients presenting with diffuse indeterminate nodules is very important. Definitive diagnosis of DPM requires histopathology and most often videothoracoscopic lung biopsy.

An unusual dyspnea in an 87-year old woman affected by Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a progressive autoimmune disease and is characterized by eye and mouth dryness due to lymphocytic infiltration in lacrimal and salivary glands leading to tissue destruction, but it can also present systemic manifestations including lung involvement. Respiratory manifestations in pSS have a prevalence of 9-20% and can be due to airway and/or lung parenchyma involvement, such as in particular in interstitial lung diseases like lymphocytic interstitial pneumonia (LIP). LIP is an inflammatory diffuse parenchymal lung disease, which is almost invariably associated with other conditions, such as autoimmune diseases and immunodeficiency states, and usually affects women with a mean age of 50 years. We described a case of patient with LIP who was referred to our Internal Medicine Unit and the diagnostic issues related to the patient age and comorbidities.

The common ABCA3E292V variant disrupts AT2 cell quality control and increases susceptibility to lung injury and aberrant remodeling

ATP binding cassette class A3 (ABCA3) is a lipid transporter that plays a critical role in pulmonary surfactant function. The substitution of valine for glutamic acid at codon 292 (E292V) produces a hypomorphic variant that accounts for a significant portion of ABCA3 mutations associated with lung disorders spanning from neonatal respiratory distress syndrome and childhood interstitial lung disease to diffuse parenchymal lung disease (DPLD) in adults including pulmonary fibrosis. The mechanisms by which this and similar ABCA3 mutations disrupt alveolar type 2 (AT2) cell homeostasis and cause DPLD are largely unclear. The present study, informed by a patient homozygous for the E292V variant, used an in vitro and a preclinical murine model to evaluate the mechanisms by which E292V expression promotes aberrant lung injury and parenchymal remodeling. Cell lines stably expressing EGFP-tagged ABCA3 isoforms show a functional deficiency of the ABCA3E292V variant as a lipid transporter. AT2 cells isolated from mice constitutively homozygous for ABCA3E292V demonstrate the presence of small electron-dense lamellar bodies, time dependent alterations in macroautophagy, and induction of apoptosis. These changes in AT2 cell homeostasis are accompanied by a spontaneous lung phenotype consisting of both age dependent inflammation and fibrillary collagen deposition in alveolar septae. Older ABCA3E292V mice exhibit increased vulnerability to exogenous lung injury by bleomycin. Collectively, these findings support the hypothesis that the ABCA3E292V variant is a susceptibility factor for lung injury through effects on surfactant deficiency and impaired AT2 autophagy.

The Diagnostic Yield of the Multidisciplinary Discussion in Patients With COVID-19 Pneumonia

Purpose: The hypothesis of the study was that a multidisciplinary approach involving experienced specialists in diffuse parenchymal lung disease might improve the diagnosis of patients with COVID-19 pneumonia.Methods: Two pulmonologists, two radiologists, and two pathologists reviewed 27 patients affected by severe COVID-19 pneumonia as the main diagnosis made by non-pulmonologists. To evaluate whether the contribution of specialists, individually and/or in combination, might modify the original diagnosis, a three-step virtual process was planned. The whole lung examination was considered the gold standard for the final diagnosis. The probability of a correct diagnosis was calculated using a model based on generalized estimating equations. The effectiveness of a multidisciplinary diagnosis was obtained by comparing diagnoses made by experienced pulmonologists with those made by non-pulmonologists.Results: In 19% of cases, the diagnosis of COVID-19-related death was mainly incorrect. The probability of a correct diagnosis increased strikingly from an undedicated clinician to an expert specialist. Every single specialist made significantly more correct diagnoses than any non-pulmonologist. The highest level of accuracy was achieved by the combination of 3 expert specialists (p = 0.0003).Conclusion: The dynamic interaction between expert specialists may significantly improve the diagnostic confidence and management of patients with COVID-19 pneumonia.