Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from a mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this clinical diversity, genetic background has often been mentioned. In parallel, recent evidence has also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed the importance of these two host-related factors in shaping the immune response in pneumoviral disease. We show that a prior gammaherpesvirus infection improves, in a genetic background-dependent manner, the immune system response against a subsequent lethal dose of pneumovirus primary infection notably by inducing a systematic expansion of the CD8+ bystander cell pool and by modifying the resident alveolar macrophages (AMs) phenotype to induce immediate cyto/chemokinic responses upon pneumovirus exposure, thereby drastically attenuating the host inflammatory response without affecting viral replication. Moreover, we show that these AMs present similar rapid and increased production of neutrophil chemokines both in front of pneumoviral or bacterial challenge, confirming recent studies attributing a critical antibacterial role of primed AMs. These results corroborate other recent studies suggesting that the innate immunity cells are themselves capable of memory, a capacity hitherto reserved for acquired immunity.

A Cross-Sectional Study of Radiological Profile of Interstitial Lung Disease Using High Resolution Computed Tomography of Patients Attending Medical College at Ahmedabad

BACKGROUND Interstitial lung disease (ILD) is an unpredictable diffuse parenchymal lung disease, which involves interstitium of lung (tissue around the alveoli of the lungs). High resolution computed tomography (HRCT) is one of the confirmatory, easily accessible methodology for the conclusion and follow up assessment of interstitial lung disease. We wanted to study the normal HRCT patterns found with interstitial lung disease and contrastingly different HRCT designs and clinical information in differential determination of pulmonary fibrosis. We also wanted to study the different patterns of interstitial lung disease on high resolution computed tomography and thereby provide accurate diagnosis and management to the patients. METHODS The study was a hospital based prospective, cross sectional study. In the present study, total fifty patients referred from Department of Medicine and Department of Pulmonary Medicine of GCS Medical College having suspicion of interstitial lung disease were studied from April 2019 to September 2019. All patients underwent HRCT thorax on 16 slice Siemens computerised tomography (CT) scan machine in recumbent position utilising usual HRCT protocol. Lung abnormalities were noticed and classified for explicit diagnosis of interstitial lung pathologies. RESULTS Most of the patients (N = 25) were found to be in the age group of 50 - 80 years (17 female & 8 male). Progressive dyspnoea (N = 47; 94 %) was the most common chief complaint. The most common form of interstitial lung disease was usual interstitial pneumonia (UIN) (N = 18; 36 %) in our study. Acute interstitial pneumonia (AIP) (N = 7; 14 %) and non-specific interstitial pneumonia, NSIP (N = 7; 14 %) were the next common interstitial lung diseases. CONCLUSIONS The most well-known interstitial lung disease seen in our examination was usual interstitial pneumonia. Cases of interstitial lung disease are on the rise. Interstitial lung disease should be ruled out in all patients with progressive dyspnoea, particularly when there are no obvious or known causes of dyspnoea. Clinical and laboratory findings, pulmonary function tests, history of exposure along with HRCT workup is indispensable for the identification or exclusion of interstitial lung disease. HRCT is also useful for the follow-up study. KEYWORDS Acute Interstitial Pneumonia (AIP), High Resolution Computed Tomography (HRCT), Interstitial Lung Disease (ILD), Nonspecific Interstitial Pneumonia (NSIP), Usual Interstitial Pneumonia (UIP)

Ameliorative Effects of Oleuropein on Lipopolysaccharide-induced Acute Lung Injury Model in Rats

Acute lung injury (ALI) is one of the most common causes of death in diseases with septic shock. Oleuropein, one of the important components of olive leaf, has antioxidant and anti-inflammatory effects. The objective of this study was to investigate the effects of oleuropein on lipopolysaccharide (LPS)-induced ALI in rats. Oleuropein was administered to rats at a dose of 200 mg/kg for 20 days and LPS was given through intratracheal administration to induce ALI. The study was terminated after 12 hours. The results showed that in the group treated with oleuropein; inflammatory cytokines and oxidative stress decreased in serum, bronchoalveolar lavage fluid (BALF), and lung tissue, and there were significant improvements in the picture of acute interstitial pneumonia (AIP) caused by LPS in histopathological examination. Based on the findings of the present study, oleuropein showed protective effects against LPS-induced ALI.

Reston virus causes severe respiratory disease in young domestic pigs

Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.

656 Time to diagnostic clarity for suspected checkpoint-inhibitor pneumonitis in patients with lung cancer

BackgroundOptimal diagnostic algorithm to differentiate checkpoint inhibitor pneumonitis (CIP) from mimics is uncertain; patients with respiratory comorbidities often receive prolonged corticosteroids until diagnostic clarification. Drawbacks to empiric use of corticosteroids include decreased immunotherapy (IO) efficacy and increased infectious risk. This retrospective study systematically collected data on patients treated for lung cancer who were suspected to have severe CIP.MethodsThis single-center retrospective cohort study collected data on all lung cancer patients who received > 1 dose of an immune checkpoint inhibitor between 6/1/18 and 2/1/20 (n=210), were subsequently hospitalized and received > 1 dose of systemic corticosteroids for any indication (n=97). Data were collected on clinical factors including comorbidities, cancer stage, IO cycles, biomarkers, diagnostic work-up, antibiotics, steroids, progression, and survival. A blinded radiologist reviewed all imaging of suspected CIP cases and categorized their radiographic patterns.ResultsIn our high-risk cohort of 97 patients, median follow-up was 23 months with progression in 54 patients (56%) at median 11 months and death in 67 patients (69%) at median 14mo. Twelve patients (12%) were suspected to have severe CIP after IO treatment for lung cancer; CIP was confirmed in 5/12 and ruled-out (mimics) in 7/12 after 30 and 3 median IO cycles, respectively. Most suspected patients underwent CXR, CTA chest, blood cultures, and received empiric antibiotics. Common radiographic patterns were ground-glass opacities, organizing pneumonia, hypersensitivity pneumonitis, and acute interstitial pneumonia/acute respiratory distress syndrome (AIP/ARDS) among confirmed cases (4/5) and ground-glass opacities, organizing pneumonias, bronchiolitis, AIP/ARDS among mimics (4/7). The median time to confirm CIP or rule out a mimic was 5 ± 4 days. Median time to onset of symptoms differed substantially for confirmed and mimic cases: 17 months and 1 month, respectively.ConclusionsCIP mimics were more common than confirmed cases in routine clinical practice, particularly among patients hospitalized for respiratory symptoms <1 month after initiating immunotherapy for lung cancers. In these cases, it is reasonable to empirically cover possible CIP with shorter (~1 week) courses of steroids until diagnostic clarity is achieved. CT imaging should be obtained as it is sensitive though not specific for CIP. CIP mimics may contribute to the higher incidence of CIP reported by real-world patient registries than by clinical trials.Ethics ApprovalThe study was approved by Wake Forest Baptist Medical Center‘s Ethics Board, IRB approval number 00044126

COVID-19: a Great Mime or a Trigger Event of Autoimmune Manifestations?

: Viruses can induce autoimmune diseases, in addition to genetic predisposition and environmental factors. Particularly, coronaviruses are mentioned among the viruses implicated in autoimmunity. Today, the world's greatest threat derives from the pandemic of a new human coronavirus, called “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), the responsible agent of coronavirus disease 2019 (COVID-19). COVID-19 originated in Wuhan, the capital of Hubei, China in December 2019 and, to date, has spread to at least 187 countries. This review focuses on autoimmune manifestations described during COVID-19, including pro-thrombothic state associated to antiphospholipid antibodies (aPL), acute interstitial pneumonia, macrophage activation syndrome, lymphocytopenia, systemic vasculitis, and autoimmune skin lesions. This offers the opportunity to highlight the pathogenetic mechanisms common to COVID19 and several autoimmune diseases, in order to identify new therapeutic targets. In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time. Hence, endothelium might represent the common pathway in which autoimmunity and infection converge. In addition, autoimmune phenomena in COVID-19 can be explained by regulatory T cells impairment and cytokines cascade.

A Rare Case of Acute Interstitial Pneumonia Diagnosed at Autopsy

Introduction/Objective Acute interstitial pneumonia (AIP) is a rare disease clinically characterized by rapidly progressing respiratory failure in individuals with no history of respiratory illness or other inciting factors. While most often diagnosed in middle-aged adults, it may present in any age group. Initial presentation is described as influenza- like, and respiratory failure requiring ventilatory support often progresses within weeks to months. Prognosis is poor, with an estimated mortality rate approaching 80% without treatment. Methods We present the case of a 44-year-old male nonsmoker with no significant medical history, who presented in 2018 with 1.5 months of dyspnea and headache initially diagnosed as atypical pneumonia. Chest imaging revealed bilateral opacities; however, microbial workup revealed no evidence of infectious etiology. Autoimmune serology studies were likewise unrevealing. Despite aggressive supportive and medical management, he deteriorated to respiratory failure and succumbed. Results At autopsy, the lungs were symmetrically congested and edematous (combined weight 2,340 g) but free of evident consolidation or discrete lesions. Microscopic examination revealed diffuse alveolar damage with extensive hyaline membrane formation, interstitial edema, and fibroblastic proliferation. The vasculature was severely congested, and the alveoli contained hemorrhage and scattered macrophages. No fungal or mycobacterial elements were identified by staining. Based on the histologic features and clinical context, the diagnosis of AIP was made. Conclusion AIP is a rare, aggressive, and diagnostically challenging disease that includes a broad range of both clinical and histologic differentials. Timely recognition and intervention with aggressive respiratory support and high- dose glucocorticoids are the mainstays of clinical management. The diagnostic role of histology is significant, but hinges on early clinical consideration of AIP as disease progression may later preclude the biopsy procedure. We share this case to raise awareness of this rapidly progressive and diagnostically troubling interstitial lung disease while emphasizing the importance of clinicopathologic correlation.