Requiring Lung Transplantation Research Articles

Carbon monoxide attenuates cellular senescence-mediated pulmonary fibrosis via modulating p53/PAI-1 pathway

PurposeIdiopathic pulmonary fibrosis (IPF) is a fatal progressive condition often requiring lung transplantation. Accelerated senescence of type II alveolar epithelial cells (AECII) plays a crucial role in pulmonary fibrosis progression through the secretion of the senescence-associated secretory phenotype (SASP). Low-dose carbon monoxide (CO) possesses anti-inflammatory, anti-oxidative, and anti-aging properties. This study aims to explore the preventive effects of CO-releasing molecule 2 (CORM2) in a bleomycin-induced pulmonary fibrosis model. MethodsWe established an pulmonary fibrosis model in C57BL/6J mice and evaluated the impact of CORM2 on fibrosis pathology using Masson's trichrome staining, fluorescence staining, and pulmonary function tests. Fibrogenic marker expression and SASP secretion in tissues and AECII cells were analyzed using qRT-PCR, Western blot, and ELISA assays both in vivo and in vitro. Additionally, we investigated DNA damage and cellular senescence through immunofluorescence and SA-β-gal staining. ResultsCORM2 showed a preventive effect on bleomycin-induced lung fibrosis by improving pulmonary function and reducing the expression of fibrosis-related genes, such as TGF-β, α-SMA, Collagen I/III. CORM2 decreased the DNA damage response by inhibiting γ-H2AX, p53, and p21. We identified PAI-1 as a new target gene that was downregulated by CORM2, and which was associated with cellular senescence and fibrosis. CORM2 effectively inhibited cellular senescence and delayed EMT occurrence in AECII cells. ConclusionOur study highlights the potential of CORM2 in preventing DNA damage-induced cellular senescence in bleomycin-induced pulmonary fibrosis through modulation of the p53/PAI-1 signaling pathway. These findings underscore the promising prospects of CORM2 in targeting cellular senescence and the p53/PAI-1 pathway as a potential preventive strategy for IPF.

Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study.

Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. A single-center retrospective cohort study. The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger (p = 0.003), had lower FVC (p < 0.001), DLCO (p < 0.001), and a higher rate of pulmonary hypertension (p = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients. There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.

Bronchopulmonary dysplasia in adults: Exploring pathogenesis and phenotype.

This review highlights both the longstanding impact of bronchopulmonary dysplasia (BPD) on the health of adult survivors of prematurity and the pressing need for prospective, longitudinal studies of this population. Conservatively, there are an estimated 1,000,000 survivors of BPD in the United States alone. Unfortunately, most of the available literature regarding outcomes of lung disease due to prematurity naturally focuses on pediatric patients in early or middle childhood, and the relative amount of literature on adult survivors is scant. As the number of adult survivors of BPD continues to increase, it is essential that both adult and pediatric pulmonologists have a comprehensive understanding of the pathophysiology and underlying disease process, including the molecular signaling pathways and pro-inflammatory modulators that contribute to the pathogenesis of BPD. We summarize the most common presenting symptoms for adults with BPD and identify the critical challenges adult pulmonologists face in managing the care of survivors of prematurity. Specifically, these challenges include the wide variability of the clinical presentation of adult patients, comorbid cardiopulmonary complications, and the paucity of longitudinal data available on these patients. Adult survivors of BPD have even required lung transplantation, indicating the high burden of morbidity that can result from premature birth and subsequent lung injury. In addition, we analyze the disparate symptoms and management approach to adults with "old" BPD versus "new" BPD. The aim of this review is to assist pulmonologists in understanding the underlying pathophysiology of BPD and to improve clinical recognition of this increasingly common pulmonary disease.

Phage Milagro: a platform for engineering a broad host range virulent phage for Burkholderia.

Burkholderia infections are a significant concern in people with CF and other immunocompromising disorders, and are difficult to treat with conventional antibiotics due to their inherent drug resistance. Bacteriophages, or bacterial viruses, are now seen as a potential alternative therapy for these infections, but most of the naturally occurring phages are temperate and have narrow host ranges, which limit their utility as therapeutics. Here we describe the temperate Burkholderia phage Milagro and our efforts to engineer this phage into a potential therapeutic by expanding the phage host range and selecting for phage mutants that are strictly virulent. This approach may be used to generate new therapeutic agents for treating intractable infections in CF patients.

Outcomes of patients with COVID-19 supported by venovenous extracorporeal membrane oxygenation for greater than 90 days

ObjectiveTo determine the characteristics and outcomes of patients requiring prolonged (>90 days) venovenous extracorporeal membrane oxygenation (VV ECMO) support for refractory Coronavirus disease 2019 (COVID-19)-associated respiratory failure. MethodsA retrospective, observational analysis of consecutive patients requiring VV ECMO for COVID-19–associated respiratory failure was performed at a single institution between March 2020 and January 2022. Data were collected from the medical records. Patients were predominantly cannulated and supported long-term with a single, dual-lumen cannula in the internal jugular vein with the tip positioned in the pulmonary artery. All patients were managed with an awake VV ECMO approach, emphasizing avoidance of sedatives, extubation, ambulation, physical therapy, and nutrition. Patients requiring >90 days of ECMO were identified, analyzed, and compared to those needing a shorter duration of support. ResultsA total of 44 patients were supported on VV ECMO during the study period, of whom 36 (82%) survived to discharge. Thirty-one patients were supported for <90 days, of whom 28 (90%) were discharged alive. Thirteen patients required >90 days of ECMO. All patients were extubated. Eight patients (62%) survived to discharge, with 1 patient requiring lung transplantation prior to decannulation. All survivors were free from mechanical ventilation and alive at a 6-month follow-up. Of the 4 patients who died on prolonged ECMO, 2 developed hemothorax necessitating surgery and 2 succumbed to fatal intracranial hemorrhage. ConclusionsPatients treated with VV ECMO for COVID-19–associated respiratory failure may require prolonged support to recover. Extubation, ambulation, aggressive rehabilitation, and nutritional support while on ECMO can yield favorable outcomes.

Lung Transplantation under a Janus Kinase Inhibitor in Three Patients with SAVI Syndrome.

Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a very rare autoinflammatory disease related to STING1 mutation. SAVI is mainly characterized by fever attacks and skin and respiratory manifestations such as interstitial lung disease or alveolar hemorrhage. Respiratory involvement occurs in 80% of cases and might progress to severe lung fibrosis and require lung transplantation (LT). Three patients with SAVI who underwent LT have been reported to date. Two of the three patients died months or years after LT due to multiple organ failure or sepsis. However, the diagnosis of SAVI was made after LT, thus preventing the use of targeted therapy, such as the Janus kinase 1 and 2 inhibitor (JAK1/2i) ruxolitinib, which might be beneficial for the respiratory status of these patients. We aimed to report our experience in managing three patients who were followed in three large lung transplantation centers in France and who benefited from ruxolitinib before undergoing LT. We describe posttransplant complications that occurred as well as outcomes.

Lung transplantation in primary pulmonary arterial hypertension and pulmonary venous hypertension.

End-stage lung disease from primary pulmonary hypertension (PPHTN) and pulmonary venous-occlusive disease (PVOD) may require lung transplantation (LT). While medical therapies exist for the palliation of PPHTN, no therapies exist for PVOD. The study's objective is to compare outcomes of LT in these patients. Patients with PPHTN and PVOD who had undergone LT were identified in the UNOS database (2005-2022). Univariable analyses compared differences between groups in demographic, clinical, and post-transplant outcomes. Multivariable logistic regression examined the association between the diagnosis group and survival. Overall survival time between groups was compared using the Kaplan-Meier method. Six hundred and ninety-six PPHTN and 78 PVOD patients underwent LT during the study period. Patients with PVOD had lower pulmonary artery mean pressure (47vs. 53mmHg, p<.001), but higher cardiac output (4.51vs. 4.31 L/min, p=.04). PVOD patients were more likely to receive lungs from donation after cardiac death donors (7.7vs. 2.9%, p=.04). There were no differences in postoperative complications or length of stay. PVOD was associated with superior survival at 30-day (100vs. 93%, p=.02) and 90-day post-transplant (93vs. 83%, p=.03), but not at later time points. In multivariable analyses, PVOD and brain death donor use were associated with better survival up to 90-day mark. Patients undergoing LT for PVOD had better initial survival, which disappeared after 1 year of transplantation. Donation after circulatory death donor use had a short-term survival disadvantage.

Pseudoaneurysm after aortopulmonary window repair and bilateral lung transplantation for eisenmenger syndrome: a case report

BackgroundAortopulmonary window (APW) is a rare congenital cardiac anomaly characterized by communication between the main pulmonary artery and ascending aorta. There are various surgical techniques, and the short- and long-term results are excellent if the surgical repair is performed early in life. To our knowledge, there have been no reports of pseudoaneurysm after APW repair. Herein, we present a case of a 30-year-old woman with an ascending aortic pseudoaneurysm found at the site of APW repair nine months after the APW repair and bilateral lung transplantation.Case presentationsA 30-year-old woman presented with APW and Eisenmenger syndrome. The patient underwent APW repair and bilateral lung transplantation. We transected the communication between the aorta and pulmonary artery and closed the aortic side directly with strips of felts. Nine months after the surgery, the patient complained of chest pain. Cardiac computed tomography revealed an ascending aortic pseudoaneurysm at the anastomotic site. Emergent graft replacement of the ascending aorta was performed and the postoperative course was uneventful.ConclusionsWe have presented a case of a pseudoaneurysm at the anastomotic site after APW repair and bilateral lung transplantation. The choice of surgical technique should be based on the patient’s background requiring lung transplantation, and in these cases close postoperative follow-up is required.

Haemodynamic, Biochemical and Respiratory Implications of total Bronchoalveolar Lavage in Pulmonary Alveolar Proteinosis

Introduction: Total bronchoalveolar lavage (BAL) continues to be the treatment of choice for alveolar proteinosis (AP), facilitating the removal of lipoprotein material. The purpose of this article is to evaluate the impact of haemodynamic, biochemical, and respiratory parameters, as well as the complications and evolution of patients undergoing this procedure. Methods: Retrospective, observational, and descriptive study of BAL. The technique was performed in the Intensive Care Unit. Blood gases, blood pressure, central venous pressure, body temperature, and fluid balance were analyzed. Results: Including eight patients, thirty-eight BAL were performed from 2008 to 2021. The mean instillation of saline at each session was 13.464 ± 4.002 ml per lung. No significant changes were observed before and after BAL in heart rate and blood pressure. Mean central venous pressure increased by 2.59 cm H20. The pO2 initial was 126 mmHg with a final mean of 69.7 mmHg, with statistical significance. The pCO2, HCO3 and pH parameters remained stable. Complications were observed during fifteen of the thirty-eight BAL (nine with arterial hypotension, three with glottic oedema, one acute pulmonary oedema, one pneumothorax, and one cardiorespiratory arrest). In terms of evolution, one case had a clinical-radiological resolution, one case of exits, one required lung transplantation, and the remaining five remained stable. Conclusion: This study demonstrates that the procedure, is well tolerated haemodynamically and that the biochemical alterations to which the patient is subjected are not compromised. With few complications and good results in delaying the progression of AP.

ISG15 Deficiency: An expanding phenotype

IntroductionISG15 is a Type I IFN-inducible intracellular protein that interacts with and stabilizes USP18, a negative regulator of IFN-I pathway, and thus acts in a negative feedback loop. Lung damage caused by pulmonary fibrosis cannot be repaired, and can require lung transplantation; therefore, a better understanding of the causes is crucial. Here, we describe the case of a 13-year-old female presented with interstitial lung disease due to a mutation in ISG15. There is an increasing number of ISG15 deficient patients who present with lung fibrosis, but the significance of ISG15 in proper wound healing and fibrosis is unknown. We aim to investigate ISG15’s role in fibrosis by studying this mutant. MethodsWhole exome sequencing and molecular cloning was performed to identify the mutation and its expressivity. INFα stimulation of cells carrying the mutation to assess differential levels of apoptosis, necroptosis and pyroptosis compared to WT cells. Scratch wound assay to assess the mutant’s ability to effectively heal a wound. Fibrosis due to the overactivation of fibroblasts to myofibroblasts due to TGFβ and IFNα exposure. ResultsThe mutation is a duplication of a cysteine at position 463 of ISG15, causing a frameshift mutation at the very end of the gene which generates an mRNA transcript without a stop codon. Further analysis revealed that even though the mutant ISG15 mRNA gets transcribed, it does not get translated (ISG15 deficiency). In-vitro experiments revealed no changed in apoptosis, necroptosis nor pyroptosis when mutant cells were treated with IFNα, but they were more sensitive to the antiproliferation effects of IFNα. Therefore, these data suggest a possible mechanism by which ISG15 deficiency could aid to lung fibrosis due to the inability of the fibroblasts to properly proliferate and heal a wound.

Intimal granulomatous angiitis in sarcoid pulmonary vasculitis: worth remembering.

Intimal granulomatous angiitis is a facet of pulmonary sarcoidosis vasculitis that has almost been forgotten. Its observation may offer new understanding of the various patterns of pulmonary hypertension associated with sarcoidosis. https://bit.ly/3g6Ms76.

Rehabilitation Characteristics and Outcomes for Lung Transplantation for COVID-19: A Case Series.

Severe coronavirus disease 2019 (COVID-19) can result in irreversible lung damage, with some individuals requiring lung transplantation. The purpose of this case series is to describe the initial experience with the rehabilitation and functional outcomes of 9 patients receiving a lung transplant for COVID-19. Nine individuals, ranging in age from 37 to 68years, received bilateral orthotopic lung transplantation (BOLT) for COVID-19 between December 2020 and July 2021. Rehabilitation was provided before and after the transplant, including in-hospital rehabilitation, postacute care inpatient rehabilitation, and outpatient rehabilitation. Progress with mobility was limited in the pretransplant phase despite rehabilitation efforts. Following transplantation, 2 individuals expired before resuming rehabilitation, and 2 others had complications that delayed their progress. The remaining 5 experienced clinically important improvements in mobility and walking capacities. Considerable rehabilitation resources are required to care for individuals both before and after BOLT for COVID-19. Rehabilitation can have a profound impact on both functional and clinical outcomes for this unique patient population. There is limited literature on the rehabilitation efforts and outcomes for patients who received BOLT for COVID-19. Occupational therapists and physical therapists play an important role during the pretransplant and posttransplant recovery process for this novel patient population. Patients with a bilateral orthotopic lung transplant due to COVID-19 require a unique rehabilitation process. They have significant difficulties with activities of daily living and functional mobility across the pretransplant and posttransplant continuum of care, but progressive gains in functional performance may be possible with a comprehensive multidisciplinary rehabilitation program.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV₁) decline and LT candidates without rapid FEV₁ decline in the last year to identify a preventable cause in patients with such rapid FEV₁ decline. All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV₁ below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV₁ decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV₁ in 2017 in Group 1 and between FEV₁ values in 2017 and 2018 in Group 2. There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Living Donor Lobar Lung Transplant for a Patient With Lung Disease Caused by ABCA3 Gene Mutations: A Case Report

Recessive gene mutations in ABCA3 cause lethal neonatal respiratory distress, and pediatric and adult interstitial lung disease. The effectiveness of medical treatments is limited and a subset of such patients will eventually require lung transplantation. A 20 months old boy developed interstitial lung disease and was treated with hydroxychloroquine, which had a significant effect. Sequence analysis of ABCA3 gene revealed newly discovered compound heterozygous mutations. His respiratory dysfunction gradually progressed over years and he underwent living-donor lobar lung transplantation (LDLLT) at 8 years of age with his parents serving as bilateral lobar donors. The parents had been genetically examined beforehand and found to be carriers who had one allele with an ABCA3 gene mutation and the other with no mutation. The recipient has been well without chronic lung allograft dysfunction and his parents have been enjoying healthy social lives for 7 years since the operations. LDLLT appears to be a valid option for selected children with ABCA3 gene mutations who are too ill to wait for cadaveric lung transplantation. When relatives of the recipient with ABCA3 gene mutation are deemed potential donors for LDLLT, sequence analyses of the donors are indispensable to exclude the possibility that they are late-onset patients of this recessive hereditary disease.

ENDOBRONCHIAL VALVES FOR TREATMENT OF PERSISTENT AIR LEAK AFTER SECONDARY SPONTANEOUS PNEUMOTHORAX IN PATIENTS WITH CYSTIC FIBROSIS

ENDOBRONCHIAL VALVES FOR TREATMENT OF PERSISTENT AIR LEAK AFTER SECONDARY SPONTANEOUS PNEUMOTHORAX IN PATIENTS WITH CYSTIC FIBROSIS

A CASE SERIES OF RAPID PROGRESSIVE FIBROTIC LUNG DISEASE AS A SEQUELA OF COVID-19 PNEUMONIA

A CASE SERIES OF RAPID PROGRESSIVE FIBROTIC LUNG DISEASE AS A SEQUELA OF COVID-19 PNEUMONIA

COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report

BackgroundAutoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections.Case presentationA 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now).ConclusionsWe report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.

Impact of gastroesophageal reflux disease on idiopathic pulmonary fibrosis and lung transplant recipients.

Idiopathic pulmonary fibrosis (IPF) is a prevalent subset of interstitial lung disease (ILD) that often progresses to require lung transplantation. Gastroesophageal reflux disease (GERD) is common in the IPF population, and GER-related micro-aspiration appears to be an important risk factor for IPF pathogenesis and for the deterioration of transplanted lung function. Many patients with IPF have elevated esophageal acid exposure on reflux testing despite having no or minimal symptoms. Studies on the effects of medical GERD therapy on IPF-related outcomes have had mixed results. Antireflux surgery is safe in appropriately selected IPF patients, and appears to have potential for slowing the decline of lung function. GERD can persist, improve or develop after lung transplantation, and the presence of GERD is associated with allograft injury and pulmonary function decline in lung transplant recipients. Clinicians should have a low threshold to assess for objective evidence of GERD in IPF patients. Antireflux surgery in IPF patients with GERD appears to improve lung function, but further studies are needed before surgical treatment can be recommended routinely in this setting. In lung transplant recipients, reflux testing after transplant is the most accurate way to guide GERD treatment decisions.

Pulmonary arterial hypertension and lung transplantation: when one severe pathology is replaced by another

Abstract Pulmonary arterial hypertension (PAH) is a rare and severe disease characterised by the progressive narrowing of the small pulmonary arteries resulting in right-sided heart failure. Despite advances in treatment, some PAH patients require lung transplantation, which carries risks of long-term complications. We report the case of a male patient with no significant comorbidities, who developed progressive dyspnoea on exertion at the age of 38 years. After echocardiography and right heart catheterisation, he was confirmed with idiopathic PAH and was started treatment with bosentan, sildenafil and beraprost. After 3 years of stability, the PAH worsened. Treatment with continuous intravenous epoprostenol was introduced in a national premiere, unfortunately with little effect. The patient underwent lung transplantation at the age of 43 years. Afterwards, he developed several complications, including chronic lung allograft dysfunction, post-transplant lymphoproliferative disorder and pulmonary embolism. He died at the age of 52 years of invasive pulmonary aspergillosis. The case is noteworthy due to the above-average post-transplant survival despite multiple complications.

Chronic COVID 19 Related Disease Requiring Lung Transplantation with Calcified Cavitary Lesions in Explanted Lungs

IntroductionBilateral cavitary lung lesions with calcification in a patient with chronic COVID requiring transplantation are described.Case Report46-year-old woman presented for lung transplant with respiratory failure due to COVID-19 pneumonia following remdesivir, decadron, tocilizumab and baricitinib therapy. Cavitary upper lobe lung lesions were noted on imaging with negative cultures. She was started on VV ECMO as a bridge to bilateral lung transplant. Explanted lungs were consolidated and fibrotic with bilateral upper lobe calcification surrounding cavitary lesions. Varied microscopic pathology included NSIP pattern of inflammation, and foci of airway centered inflammation with giant cells suggesting chronic hypersensitivity reaction. The calcification was reminiscent of dendriform/metastatic calcification, and involved areas of necrotic/mummified parenchyma.SummaryCavitation as a late stage complication of COVID19 has been described in rare cases and is considered atypical. The constellation of findings in our case, including cavitary lesions with associated dendriform like calcifications are unique and maybe attributable to COVID19 itself +/- exacerbation of underlying chronic lung disease +/- intercurrent infection, or COVID19 related cavitation with superimposed secondary changes due to ECMO treatment. Bilateral lung transplantation has a reasonable short-term prognosis for patients with end stage respiratory failure secondary to COVID19; examination of these native lungs may expand our concept of COVID19 related chronic lung injury patterns.