Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study.

BACKGROUND: Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis. METHODS: Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks. RESULTS: After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased (p<0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group (p=0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting. CONCLUSION: In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.

Anti-fibrotic agents could be the game-changer for post-COVID-19 pulmonary fibrosis treatment

More than 220 countries and territories are globally affected by the recent pandemic COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is possibility of third wave of this pandemic as per epidemiological and public health experts. Besides that post-COVID-19 complications are alarming matter to look upon. Post-COVID-19 complications include several symptoms like as persistent fever;cough;fatigue;headache;attention disorder;dyspnea;anosmia;ageusia;chest pain discomfort;various respiratory illness;acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19. In some COVID-19 patients, hyper-inflammation in the form of 'cytokine storm' along with dysregulated immune response, alveolar epithelial tissue injury and wound repair collectively cause this secondary pulmonary fibrosis. Therefore, using anti-fibrotic agents e.g. pirfenidone, nintedanib and other natural compounds could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article, we have discussed the progression of pulmonary fibrosis development which is triggered by COVID-19;probable solutions with anti-fibrotic agents including anti-fibrotic drugs, some well-known natural compounds, combined anti-fibrotic therapies;and the current challenges of this field.

Pirfenidone Induced Dress Syndrome Post COVID-19 Infection-An Unusual Case Report

Drug Reaction, Eosinophilia and Systemic Symptoms (DRESS) is an idiosyncratic drug reaction characterised by extensive skin rash, fever, lymphadenopathy and internal organ involvement. Since eosinophilia may or may not always be present, the condition is now more preferably called Drug-Induced Hypersensitivity Syndrome (DIHS). The authors here report a case of DRESS syndrome, secondary to Pirfenidone, an anti-fibrotic given to the patient for post COVID-19 fibrosis. The 51 years old male patient, presented with multiple pus-filled erythematous lesions, 3 months after the initiation of Pirfenidone. Laboratory results showed deranged liver and renal functioning, along with reactive Dengue Nonstructural protein 1(NS 1) antigen. He showed significant improvement in the dermatological lesions and multisystem laboratory involvement with tapering doses of steroids.

Incidence of acute exacerbation in patients with interstitial lung disease after COVID-19 vaccination

Acute exacerbations due to COVID-19 vaccination in patients with interstitial lung disease (ILD) have been reported, but their incidence is unknown. We investigated the incidence of exacerbations of ILD and respiratory symptoms due to the mRNA COVID-19 vaccines. A questionnaire survey was conducted on adverse reactions to the mRNA COVID-19 vaccination in 545 patients with ILD attending our hospital and retrospectively examined whether the eligible patients actually developed acute exacerbations of ILD induced by the vaccine. Of the 545 patients, 17 (3.1%) patients were aware of the exacerbation of respiratory symptoms, and four (0.7%) patients developed an acute ILD exacerbation after vaccination. Of the four patients who experienced exacerbations, two had collagen vascular disease-associated ILD, one had nonspecific interstitial pneumonia, another had unclassifiable idiopathic pneumonia, and none had idiopathic pulmonary fibrosis. Four patients were treated using steroid pulse therapy with a steroid taper, and two of the four also received intravenous cyclophosphamide pulse therapy. Tacrolimus was started in one patient with myositis-associated interstitial lung disease. Eventually, all patients exhibited improvement with immunosuppressive treatment and were discharged. COVID-19 vaccination for patients with ILD should be noted for developing acute exacerbations of ILD with low incidence, although manageable with early diagnosis and treatment. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

A Study on drug utilization pattern of antifibrotic agents in patients with post-COVID-19 lung fibrosis

Pulmonary fibrosis after COVID-19 is a serious consequence that can result in lifelong lung damage or death. A cytokine storm induced by an abnormal immune mechanism may cause the onset and progression of pulmonary fibrosis. Early detection may assist to avoid or at least slow the progression of the disease. Anti-fibrotic agents are widely used drugs in post-COVID-19 pulmonary fibrosis. There are some well-known clinical agents including Pirfenidone and Nintedanib that can be given to COVID-19 patients to prevent further progression of fibrosis and as prophylaxis as well. This study showed the use of antifibrotic therapy in SARS-CoV-2 infection, which is very officious in minimizing and avoiding fibrotic damage induced by inflammatory immune dysfunction. Evidently, pirfenidone has shown its pleiotropic effectivity to decrease the inflammation and oxidative reactive shock associated with fibrosis. Nintedanib binds to the targeted receptors' intracellular ATP pockets, inhibiting pro-fibrotic signaling and reducing fibroblast proliferation, migration, and differentiation, as well as secretion of extracellular matrix components. Copyright © 2023, Anka Publishers. All rights reserved.

Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.

OBJECTIVES: Severe stages of COVID-19 infection have been associated with the excessive discharge of pro-inflammatory mediators such as cytokines, resulting in lung deterioration, which progresses rapidly to lung fibrosis leading to acute respiratory distress syndrome. In this investigation, the efficacy and safety of the novel antifibrotic and anti-inflammatory agent, Pirfenidone, were assessed in COVID-19 patients with pulmonary fibrosis secondary to cytokine storm. In this randomized controlled study, we assigned 100 adult COVID-19 patients cytokine storm and admitted to the intensive care isolation unit into either pirfenidone added to the standard therapy (n = 47), or the standard protocol only (n = 53). High-resolution computed tomography of the chest was performed in all patients to evaluate fibrotic lesions and their progression. The results showed that the percentage of patients who developed pulmonary fibrosis during cytokine storm onset in the pirfenidone group relative to the standard group was 29.8% and 35.8%, respectively, with no significant difference between the two groups; while there was a significant increase in the proportion of patients discharged from the isolation unit with pulmonary fibrosis without progression in fibrotic lesions in the pirfenidone group compared to the standard group (21.3% and 5.7%, respectively). Furthermore, there was a significant difference concerning liver enzyme elevation and GIT disturbance incidences in the studied groups (p = 0.006 and 0.01, respectively). Our findings show that Pirfenidone inhibits fibrosis advancement in COVID-19 patients with pulmonary fibrosis and is associated with hepatotoxicity and GI distress. It may be beneficial in patients with mild to moderate COVID-19-induced pulmonary fibrosis; however, additional research is necessary.

The effect of Pirfenidone on pulmonary function parameters in post recovery COVID-19 patients with pulmonary fibrosis compared to placebo in a Government Medical College, West Bengal

Introduction and Aim: The recent COVID 19 pandemic has created an unprecedented challenge to the entire global healthcare system by affecting many people worldwide. Post COVID complications are multi-systemic, but pulmonary post COVID complications are most common. Involvement of the lung parenchyma ultimately leads to pulmonary fibrosis in many of the patients. Pirfenidone is a widely used antifibrotic medication in the field of idiopathic pulmonary fibrosis (IPF) management. Our study has assessed the effect of Pirfenidone on spirometry parameters in post recovery COVID 19 patients with diagnosed pulmonary fibrosis as compared to those that received placebo. Material(s) and Method(s): After obtaining approval from Institutional Ethics Committee, 70 adult patients of COVID-19 with established pulmonary fibrosis in the post recovery phase were chosen and allocated into two groups by randomization in 1:1 ratio. All other factors remaining same, one group was administered the recommended dose of Pirfenidone and the other group received a placebo. Spirometry parameters such as FEV1, FEV1 /FVC ratio, FVC, PEFR of both the groups were recorded on Day 0 and Day 90 and compared using standard statistical tests. Result(s): It was found that on Day 0, PFT parameters of the two groups was comparable (P value>0.05). PFT parameters of the group receiving Pirfenidone showed significant improvement on day 90 (P value<0.05). In addition, on day 90, the PFT parameters of the group receiving Pirfenidone showed significantly better values than the group receiving placebo, P value <0.05. Conclusion(s): As there is a significant improvement in the PFT parameters of post recovery COVID-19 patients suffering from pulmonary fibrosis, we conclude that Pirfenidone is helpful to improve the pulmonary function parameters in post recovery COVID-19 patients with established lung fibrosis as compared to placebo. Copyright © 2022, Indian Association of Biomedical Scientists. All rights reserved.

Effectiveness and Safety of Pirfenidone and Nintedanib for Pulmonary Fibrosis in COVID-19-Induced Severe Pneumonia: An Interventional Study.

Background After a diagnosis of two to five years, the survival length for pulmonary fibrosis (PF) is considered to be medium. The primary objective of PF treatment is to stabilize or minimize the pace of progression of the illness. The treatment of PF by nintedanib and pirfenidone was a breakthrough. In a group of coronavirus disease 2019 (COVID-19)-induced PF patients, we examined the efficacy of pirfenidone and nintedanib. Methodology From May 2021 to April 2022, 5,000 patients receiving antifibrotic treatment with pirfenidone or nintedanib (mean age of 78.3 ± 23.8) for PF were identified. Their clinical and functional information was retrospectively examined at zero, six, and twelve months of therapy. Results The average age of patients receiving nintedanib was greater than the average age of the pirfenidone group (p < 0.0001). Exertional dyspnea and dry cough, with no distinction between the two groups, were the most prevalent symptoms of the illness (p < 0.05). No significant changes between patients on pirfenidone and nintedanib were seen in forced vital capacity, forced expiratory volume in one second, total lung capacity, and diffusing capacity for carbon monoxide at zero or six months (p > 0.05). After one year, lung function measures were similar to the baseline in individuals treated with pirfenidone and nintedanib. This study highlights the appearance of both antifibrotic medicines as promising treatment options for functional stability in COVID-19-induced PF patients. Conclusions The patients affected by COVID-19 and undergoing fibrinolytic therapy may be well treated by any of the drugs with a significant improvement.

Case Report: Pirfenidone in the Treatment of Post-COVID-19 Pulmonary Fibrosis.

Background: Pulmonary fibrosis is one of the sequelae of the COVID-19, which seriously affects the quality of life of survivors. Currently, there are no optimal evidence based guidelines targeting this population. Case Presentation: We report a 66-year-old female patient without underlying comorbidities admitted to Changsha Public Health Center because of COVID-19. During hospitalization, she developed co-bacterial infection and acute respiratory distress syndrome, and received broad-spectrum antibacterial therapy, invasive mechanical ventilation and extracorporeal membrane oxygenation. After the acute phase, she developed post-COVID-19 pulmonary fibrosis subsequently treated with pirfenidone. Over 96 weeks after pirfenidone treatment, her modified Medical Research Council Dyspnea level improved to 2 from 4 at discharge. Her 6 minutes walk test distance, total lung capacity, and diffusion capacity for carbon monoxide all increased. Chest CT performed on 2 years after illness onset showed regressing fibrosis. The Hospital Anxiety and Depression Scale, Athens Insomnia Scale, and 36-Item Short Form Health Survey questionnaire all improved. Conclusion: Post-COVID-19 pulmonary fibrosis is a challenging consequence of COVID-19, and our case suggests that pirfenidone may be an effective treatment option.

Role of Antifibrotic Therapy in Pulmonary Fibrosis Due to COVID-19

Background: It has been more than year of beginning of COVID-19 outbreak, the most serious complication of COVID infection is excessive increase in inflammatory mediators also known as cytokine storm which leads to formation of pneumonia in some patients. After resolution of pneumonia some amount of fibrosis develops which leads to decrease in quality of life and increased mortality. Nevertheless, in elderly patients a small % of fibrosis can be fatal. Therefore, as corona virus has affected several millions of people even though pulmonary fibrosis being a rare complication can cause huge no. of cases of pulmonary fibrosis, Several randomized control trials has been carried out till now for treatment of fibrosis, Perfenidone and nintedanib are approved as a treatment modality of idiopathic pulmonary fibrosis, it has been also useful in non-idiopathic pulmonary fibrotic diseases like interstitial idiopathic fibrosis studies are going out for effectiveness in post COVID pulmonary fibrosis. Several other modalities are also being tested, drugs which help in decreasing the severity of cytokine storm such as steroids. Viral load can be decreased by using antiviral agents. Certain novel drugs are also being researched upon, so in this review article considering the impact of fibrosis on the covid population, cause of pulmonary fibrosis, prevention and treatment modalities has been discussed.

When and how important is anti-fibrotic therapy in the post-COVID-19 period?

PURPOSE: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. In our study, we aimed to examine the efficacy of anti-fibrotic therapy in patients who developed pulmonary fibrosis after COVID-19. METHODS: In total, 15 patients who applied to the Post-Covid Outpatient Clinic between May 2021 and August 2021 and were diagnosed with COVID-19 pneumonia, and whose cough, dyspnea, exertional dyspnea and low saturation continued to be present at least 12 weeks after the diagnosis, were included in the study. Off-label pirfenidone treatment was started according to the radiological findings, pulmonary function test parameters (PFT) and 6-minute walking test (6MWT) results. The patients were followed up for 12 weeks. RESULTS: While all of the FVC, FVC%, FEV1, FEV1%, DLCO%, DLCO/VA%, 6MWT, and room air saturation levels were observed to increase statistically significantly in the patients at the 12th week, it was determined that there was a statistically significant decrease in the pulse level in room air (p = 0.01, 0.01, 0.01, 0.01, 0.004, 0.001, 0.002, 0.001, and 0.002, respectively). In regression analysis based on radiological scoring, it was observed that the DLCO and room air saturation levels at the 12th week of the treatment were statistically significantly higher in patients with lower scores at the beginning (p = 0.04, 0.03). In addition, it was observed that anti-fibrotic treatment, which was started in the earliest period, i.e., 12 weeks after the diagnosis, resulted in an improvement in radiological, PFT and 6MWT parameters. CONCLUSION: Patients who still had dyspnea and low saturation 12 weeks after the diagnosis, defined as chronic COVID-19, should be evaluated for anti-fibrotic therapy after the necessary radiological and PFT evaluation. Early treatment commencement brings about, besides radiological improvement, a better response obtained in PFT and 6MWT (Tab. 2, Fig. 2, Ref. 21).

Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals.

Pirfenidone (PFN) is an anti-fibrotic drug with significant anti-inflammatory property used for treatment of fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). In the coronavirus disease 2019 (Covid-19) era, severe acute respiratory syndrome 2 (SARS-CoV-2) could initially lead to acute lung injury (ALI) and in severe cases may cause acute respiratory distress syndrome (ARDS) which is usually resolved with normal lung function. However, some cases of ALI and ARDS are progressed to the more severe critical stage of pulmonary fibrosis commonly named post-Covid-19 pulmonary fibrosis which needs an urgent address and proper management. Therefore, the objective of the present study was to highlight the potential role of PFN in the management of post-Covid-19 pulmonary fibrosis. The precise mechanism of post-Covid-19 pulmonary fibrosis is related to the activation of transforming growth factor beta (TGF-ß1), which activates the release of extracellular proteins, fibroblast proliferation, fibroblast migration and myofibroblast conversion. PFN inhibits accumulation and recruitment of inflammatory cells, fibroblast proliferation, deposition of extracellular matrix in response to TGFß1 and other pro-inflammatory cytokines. In addition, PFN suppresses furin (TGFß1 convertase activator) a protein effector involved in the entry of SARS-CoV-2 and activation of TGFß1, and thus PFN reduces the pathogenesis of SARS-CoV-2. Besides, PFN modulates signaling pathways such as Wingless/Int (Wnt/ß-catenin), Yes-Associated Protein (YAP)/Transcription Co-Activator PDZ Binding Motif (TAZ) and Hippo Signaling Pathways that are involved in the pathogenesis of post-Covid-19 pulmonary fibrosis. In conclusion, the anti-inflammatory and anti-fibrotic properties of PFN may attenuate post-Covid-19 pulmonary fibrosis.

Nintedanib vs pirfenidone in the management of COVID-19 lung fibrosis: A single-centre study.

BACKGROUND: COVID-19 pneumonia is complicated with residual lung fibrosis, as evidenced by imaging and postmortem pathological findings. In addition to steroids, we compared the efficacy of nintedanib and pirfenidone in the management of COVID-19 lung fibrosis measured by CT severity score (CTSS). METHODS: All cases of COVID-19 pneumonia diagnosed as COVID-19 positive by RT-PCR having SpO2 ⩽ 96% and CTSS ⩾ 10 even after 15 days were included in the study. The patients were divided into three groups. All three groups received steroids at a dose of 1 mg/kg body weight of prednisolone or equivalent. The first group received steroids alone, the second group received pirfenidone with steroids and the third group received nintedanib with steroids. All patients were followed up at 6 and 12 weeks. The primary endpoint of our study was to find out any improvement in CTSS. RESULTS: Out of 90 patients, 56 patients completed the study. Among three groups, 19 (33.9%) patients received steroids (control) only, 16 (28.6%) patients received steroids with pirfenidone and 21 (37.5%) patients received steroids with nintedanib. The study population had a mean (±SD) age of 52.5 ± 10.1 years, mean (±SD) C-reactive protein of 97.1 ± 102.2 mg/L (normal <6 mg/L), mean (±SD) serum ferritin 459.4 ± 305.5 ng/mL (normal <250 ng/mL), mean (±SD) serum d-dimer level 2.1 ± 2.6 µg/mL (normal <0.5 µg/mL) and mean (±SD) CTSS of 16.9 ± 4.3. There was significant improvement in CTSS in group receiving nintedanib compared to pirfenidone at 12 weeks (3.67 ± 1.21 vs 9.07 ± 1.12) with a p-value <0.01. CONCLUSION: Along with steroids in the treatment of COVID-19 lung fibrosis, there was a significant improvement in lung CTSS with nintedanib compared to pirfenidone.

Randomized, Double-Blind Trial of the Efficacy and Safety of Pirfenidone in Patients with Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients.Methods: In a phase 2 double-blind, single-center trial, we randomly assigned, in a 2:1 ratio, adults with FHP to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. Patients had to have CT lung fibrotic abnormalities affecting ≥5%, worsening respiratory symptoms, and either an increase in the extent of fibrosis on CT or relative decline in the FVC% of ≥5% within the 24-months before screening. The primary endpoint was the mean change from baseline to week 52 in %FVC. Secondary endpoints included progression-free survival (PFS, time to the first occurrence of any one of the following: a relative decline of ≥10% in FVC and/or DLCO, acute exacerbation, a decrease of ≥50 m in the 6-minute walk distance, increase in background prednisone by ≥10 mg or introduction of corticosteroids and/or steroid-sparing drugs, or death), change from baseline to week 52 in FVC slope and mean %DLCO, all-cause hospitalizations, CT progression of lung fibrosis, and safety. Results: After 40 patients had been randomized (mean age 67.1 years, 42.5% males) the study was stopped due to slow recruitment due to the COVID-19 pandemic. At baseline, demographics, smoking and inciting antigen exposure history, lung function, 6-minute walk distance, extent of CT lung fibrosis, and immunosuppressive therapy were balanced in both groups. There was no significant difference between the pirfenidone and placebo groups after adjusting for baseline %FVC and concomitant immunosuppressive therapy (p=0.88) in mean change from baseline to week 52 in %FVC. Secondary endpoints showed no difference between groups in change from baseline to week 52 in FVC slope, mean %DLCO, all-cause hospitalization and CT progression of lung fibrosis. However, a decrease in PFS favored pirfenidone (Table). The percentages of patients with any adverse events (AE) were similar in both groups. Nausea and rash, respectively, led to transient dose reduction of study treatment in 2 patients in the pirfenidone group. There were no treatment-related serious AE or AE leading to discontinuation of study treatment. No death occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. Conclusions: The trial was under powered to detect a difference in the primary endpoint. Pirfenidone was found to be tolerable and safe and compared to placebo reduced PFS in patients with FHP.

Liver Injury with Nintedanib: A Pharmacovigilance-Pharmacokinetic Appraisal.

Drug-induced liver injury (DILI) with nintedanib has emerged as an adverse event of special interest in premarketing clinical trials. We characterized DILI with nintedanib in the real world and explored the underlying pharmacological basis. First, we assessed serious hepatic events reported to the Food and Drug Administration's Adverse Event Reporting System by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment. Demographic and clinical features were inspected (seriousness, onset, discontinuation, dechallenge/rechallenge, concomitant drugs) to implement an ad hoc causality assessment scoring system. Second, we appraised physiochemical and pharmacokinetic parameters possibly predictive of DILI occurrence. Significant disproportionality was found for nintedanib as compared to pirfenidone (N = 91; ROR = 4.77; 95% CI = 3.15-7.39). Asian population, low body weight (59 kg), and rapid DILI onset (13.5 days) emerged as clinical features. Hospitalization and discontinuation were found in a significant proportion of cases (32% and 36%, respectively). In 24% of the cases, at least two potentially hepatotoxic drugs (statins, proton pump inhibitors, antibiotics) were recorded. Causality was at least possible in 92.3% of the cases. High lipophilicity and predicted in silico inhibition of liver transporters emerged as potential pharmacokinetic features supporting the biological plausibility. Although causality cannot be demonstrated, clinicians should consider early monitoring and medication review on a case-by-case basis.

COVID 19 pneumonias with negative rt-PCR testing

Background: The COVID 19 pandemic caused by the betacoronavirus SARS-CoV-2 with its virulence and contagiousness is a public health emergency. The prefferred method of diagnosis is the FDA aprroved RT-PCR testing of nasopharyngeal swabs with 65% sensitivity, with false negative rates of <5% to 40%. Clinical diagnosis should supplant when there is high suspicion with labs and imaging consistent with COVID'19 and negative RT-PCR does not rule out the disease. Here we report one such case. Case Report: 45-year-old female with nil comorbidities presented with fever and breathlessnesss since 7 days with tachypnoea (46 breaths/min), hypoxia (spo2 75% room air) and bilateral coarse crepitations on auscultation. ABG & CXR suggested severe ARDS. CT Thorax revealed CTSI 21/25.CORADS 5.Two nasopharyngeal swabs 24 hours apart tested negative for COVID'19. Lab investigations suggested deranged inflammatory markers (ferritin 910ng/mL;CRP 121.2ng/L ;D-dimer 660ng/mL). Presumed diagnosis of COVID 19 was established based on early CT findings and lab parameters consistent with COVID'19 Pneumonitis,the patient was immediately isolated and received treatment as per COVID'19 treatment protocols (steroids,LMWH,Remdesivir). After 6th week patient showed clinical and radiological improvement.Subsequently she also developed postcovid fibrosis and discharged on pirfenidone and home based low-flow o2. Discussion and Conclusion: Fever, sore throat and breathlessness are common symptoms of Covid'19, most of which are virtually present in any viral LRTI, however in the setting of current pandemic maintain high index of suspicion for Covid'19 especially in the presence of radiological evidence even with negative RT-PCR.

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

In this work, we studied the effect of as on the interaction of membrane DPPC with the key antifibrotic drug pirfenidone. Liposomal forms of pirfenidone were obtained using passive loading. The addition of cholesterol reduces the loading efficiency of pirfenidone by 10%. The main binding site of pirfenidone in DPPC liposomes is the carbonyl group: the interaction with PF significantly increases the proportion of low-hydrated carbonyl groups as revealed by ATR-FTIR spectroscopy. The phosphate group acts as an additional binding site;however, due to shielding by the choline group, this interaction is weak. The hydrophobic part of the bilayer is not involved in PF binding at room temperature. Cholesterol changes the way of interaction between carbonyl groups and pirfenidone probably because of the formation of two subpopulations of DPPC and causes a dramatic redistribution of carbonyl groups onto the degrees of hydration. The proportion of moderately hydrated carbonyl groups increases, apparently due to the deepening of pirfenidone into the circumpolar region of the bilayer. For the first time, a change in the microenvironment of pirfenidone upon binding to liposomes was shown: aromatic moiety interacts with the bilayer.

Pirfenidone ameliorates early pulmonary fibrosis in LPS-induced acute respiratory distress syndrome by inhibiting endothelial-to-mesenchymal transition via the Hedgehog signaling pathway.

Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases. However, the role of PFD in the course of EndMT in LPS-induced ARDS remains poorly understood. The purpose of this study was to explore the anti-EndMT effects of PFD on pulmonary fibrosis after LPS-induced ARDS. First, we determined that PFD significantly reduced LPS-induced ARDS, as shown by significant pathological alterations, and alleviated the oxidative stress and inflammatory response in vitro and in vivo. Furthermore, PFD decreased pulmonary fibrosis in LPS-induced ARDS by inhibiting EndMT and reduced the expression levels of Hedgehog (HH) pathway target genes, such as Gli1 and α-SMA, after LPS induction. In summary, this study confirmed that inhibiting the HH pathway by PFD could decrease pulmonary fibrosis by downregulating EndMT in LPS-induced ARDS. In conclusion, we demonstrate that PFD is a promising agent to attenuate pulmonary fibrosis following ARDS in the future.

A multicenter survey study of antifibrotic use for symptomatic patients with post-COVID-19 interstitial lung abnormalities.

Background: Little data exist on antifibrotic drugs for treating symptomatic patients with persistent interstitial lung abnormalities in the postacute phase of coronavirus disease 2019 (COVID-19). Herein, we describe the physician practices of prescribing pirfenidone and nintedanib for these patients and the physician-assessed response. Materials and Methods: This was a multicenter, retrospective survey study of subjects administered pirfenidone or nintedanib for post-COVID-19 interstitial lung abnormalities. Data on the demographic details, comorbidities, abnormalities on the computed tomography (CT) of the chest, treatment, antifibrotic drug use, and physician-assessed response were collected on a standard case record pro forma. We explored physician practices of prescribing antifibrotics (primary objective) and the physician-assessed response (secondary objective). Results: We included 142 subjects (mean age, 55.9 years; 16.2% women) at eight centers. The most common abnormalities on CT chest included ground glass opacities (75.7%), consolidation (49.5%), reticulation (43.9%), and parenchymal bands (16.8%). Of the 5701 patients discharged after hospitalization at six centers, 115 (2.0%) received antifibrotics. The drugs were prescribed an average of 26 days after symptom onset. One hundred and sixteen subjects were administered pirfenidone; 11 (9.5%) received the full dose (2400 mg/day). Thirty subjects were prescribed nintedanib; 23 (76.7%) received the full dose (300 mg/day). Of 76 subjects with available information, 27 (35.6%) and 26 (34.2%) had significant or partial radiologic improvement, respectively, according to the physician's assessment. Conclusions: Antifibrotic agents were administered to a minority of patients discharged after recovery from acute COVID-19 pneumonia. Larger, randomized studies on the efficacy and safety of these agents are required.