Pattern Of Lung Injury Research Articles

ALTERAÇÕES HISTOPATOLÓGICAS NO SISTEMA RESPIRATÓRIO EM DECORRÊNCIA DO USO DE CIGARRO ELETRÔNICO

ABSTRACT - Introduction: The electronic cigarette was developed as an alternative to the conventional cigarette. Its mechanism of action involves the inhalation of numerous substances that are associated with a potential for cytotoxicity leading to histopathological changes in the respiratory system. Objective: To review scientific literature on histopathological changes in the respiratory system induced by EC substances. Methods: Literature review, with a search for articles in the PubMed, Scielo and Google Scholar databases between July and October 2023. The search was carried out with 19 articles from 2019 to 2023, using the descriptors: “histology”, “e-cigarettes” and “lung injuries”. Results: Vaping contains propylene glycol, vegetable glycerin, vitamin E acetate and nicotine, substances that causes damage to the respiratory system. Tissue studies in different histological stains showed: exposure to infiltration of inflammatory cells, aggregation of macrophages, granulomatous inflammation and significant hyperplasia of mucosal cells in groups that obtained the substance propylene glycol and vitamin E acetate. In relation to the cytological preparation of bronchoalveolar lavage, inflammatory cells were found leading to endogenous lipoid pneumonia. Other tests revealed a pattern of acute lung injury - diffuse alveolar damage and acute fibrinous and organizing pneumonia. Other research has noted that vitamin E acetate acts on surfactant, preventing it from maintaining the surface tension of the pulmonary alveoli. In the case of nicotine use, exposure to nicotine causes apoptosis and the release of inflammatory proteins, leading to the infiltration of inflammatory cells in the mucosa, submucosa and glandular tissue of the airways. Conclusion: The literature shows that the use of electronic cigarettes is harmless to the body. The changes reported range from hyperplasia of the respiratory epithelium, inflammatory changes, lipoid pneumonia, acute pneumonia and diffuse alveolar damage, among others. KEYWORDS – Histology. Electronic Cigarette. Respiratory System.

683: Patterns of CT lung injury after SABR for primary or secondary lung lesions

683: Patterns of CT lung injury after SABR for primary or secondary lung lesions

Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study

BackgroundA usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid...

The scene of lung pathology during PRRSV-1 infection.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases for the pig industry worldwide. The disease was firstly reported in 1987 and became endemic in many countries. Since then, outbreaks caused by strains of high virulence have been reported several times in Asia, America and Europe. Interstitial pneumonia, microscopically characterised by thickened alveolar septa, is the hallmark lesion of PRRS. However, suppurative bronchopneumonia and proliferative and necrotising pneumonia are also observed, particularly when a virulent strain is involved. This raises the question of whether the infection by certain strains results in an overstimulation of the proinflammatory response and whether there is some degree of correlation between the strain involved and a particular pattern of lung injury. Thus, it is of interest to know how the inflammatory response is modulated in these cases due to the interplay between virus and host factors. This review provides an overview of the macroscopic, microscopic, and molecular pathology of PRRSV-1 strains in the lung, emphasising the differences between strains of different virulence.

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.

Identifying interstitial lung disease associated chemicals by integrating transcriptome-wide association study and chemical-gene interaction networks.

Interstitial lung diseases (ILD) comprise a heterogeneous group of lung disease characterized by common clinical syndromes and patterns of lung injury which poses growing burden on the health and social economic consequences. Its etiology remains elusive. By integrating transcriptome-wide association studies analysis of ILD and chemical-gene interaction networks implemented by CGSEA software, we systematically evaluated the association between ILD and 11,190 chemicals in this study. We detected several chemicals significantly associated with ILD (permutated empirical P values < 0.05). Briefly, a total of 56 chemicals were detected for ILD in lung tissue, 121 in whole blood respectively. Among the chemicals identified for ILD in lung tissue and whole blood, we found 7 common chemicals, including St. Thomas' Hospital cardioplegic solution, cytarabine, ginsenoside Rg3, cholecalciferol, fluoxetine, oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and excitatory amino acid agonists. Our findings shed lights on the underlying impact of chemical exposure on the development and progression of ILD, which will pave the way for more effective prevention and treatment strategies, ultimately improving the health outcomes and quality of life of those affected by ILD.

Radiological Patterns of Lung Injury on HRCT in COVID-19 Patients: An Experience From Tertiary Care Centre in India

Radiological Patterns of Lung Injury on HRCT in COVID-19 Patients: An Experience From Tertiary Care Centre in India

Pulmonary phenotypes of bronchopulmonary dysplasia in the preterm infant

Bronchopulmonary dysplasia (BPD) remains the most common complication of premature birth, imposing a significant and potentially life-long burden on patients and their families. Despite advances in our understanding of the mechanisms that contribute to patterns of lung injury and dysfunctional repair, current therapeutic strategies remain non-specific with limited success. Contemporary definitions of BPD continue to rely on clinician prescribed respiratory support requirements at specific time points. While these criteria may be helpful in broadly identifying infants at higher risk of adverse outcomes, they do not offer any precise information regarding the degree to which each compartment of the lung is affected. In this review we will outline the different pulmonary phenotypes of BPD and discuss important features in the pathogenesis, clinical presentation, and management of these frequently overlapping scenarios.

Blast Lung Injury in Children: Injury Patterns and Associated Organ Injuries.

Bombings are the most common cause of civilian deaths in wars, and unfortunately, a large proportion of civilian victims are children. This study aimed to evaluate the frequency of blast lung injury (BLI), to evaluate lung injury patterns on tomographic images, and to document the relationship between blast lung and mortality in children exposed to the blast effect. Thirty-six children (25.3% of pediatric patients brought to our hospital with blast injury) with BLI were included in the study. The pediatric trauma score evaluations made in the emergency department in the first admission were recorded. Lung injury findings in the computed tomography images of the patients were examined, and injuries detected in other systems were recorded. The most common lung injury pattern was contusion (right: 69.4%, left: 80.6%). The incidence of brain damage (52.4%) and intra-abdominal injury (76.2%) in children with low pediatric trauma score value was statistically significantly higher ( P = 0.049, P = 0.017, respectively). There was no statistically significant correlation between the presence of lung injury, injury patterns, and mortality. The incidence of brain damage in deceased patients (61.5%) was statistically significantly higher than the incidence of brain damage in surviving patients (26.1%) ( P = 0.036). Low pediatric trauma score was observed in 11 (84.6%) of the deceased children and in 10 (43.5%) of the survivors ( P = 0.016). The mean age of children with hemothorax in the right lung was statistically significantly lower than those without ( P = 0.014). Our findings revealed that pediatric BLI is common after a blast, that it is associated with other system injuries, and that a multimodal radiological approach is required in child victims.

Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute Respiratory Failure.

Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center. U.S. ICUs, 1996-2021. Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. None. Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.

Invited Commentary: Patterns of Lung Injury and the Challenging Role of the Radiologist

HomeRadioGraphicsVol. 43, No. 7 PreviousNext Chest ImagingInvited Commentary: Patterns of Lung Injury and the Challenging Role of the RadiologistSeth Kligerman , Teri Franks, Jeff GalvinSeth Kligerman , Teri Franks, Jeff GalvinAuthor AffiliationsFrom the Department of Radiology, National Jewish Health, 1400 S Jackson St, Denver, CO 80209 (S.K.); Division of Pulmonary and Mediastinal Pathology, The Joint Pathology Center, Joint Task Force, Defense Health Agency, Silver Spring, Md (T.F.); and Departments of Diagnostic Radiology and Nuclear Medicine and Internal Medicine (Pulmonary/Critical Care), University of Maryland School of Medicine, Baltimore, Md (J.G.).Address correspondence to S.K. (email: [email protected]).Seth Kligerman Teri FranksJeff GalvinPublished Online:Jun 8 2023https://doi.org/10.1148/rg.230013MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In

Lung pathology of natural Babesia rossi infection in dogs.

A proportion of Babesia rossi infections in dogs are classified as complicated and one of the most lethal complications is acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Most dogs that die succumb within 24 hours of presentation. The pulmonary pathology caused by B. rossi in dogs has not been described. The aim of this study was to provide a thorough macroscopic, histological and immunohistochemical description of the lung changes seen in dogs naturally infected with B. rossi that succumbed to the infection. Death was invariably accompanied by alveolar oedema. Histopathology showed acute interstitial pneumonia characterised by alveolar oedema and haemorrhages, with increased numbers of mononuclear leucocytes in alveolar walls and lumens. Intra-alveolar polymerised fibrin aggregates were observed in just over half the infected cases. Immunohistochemistry showed increased numbers of MAC387- and CD204-reactive monocyte-macrophages in alveolar walls and lumens, and increased CD3-reactive T-lymphocytes in alveolar walls, compared with controls. These histological features overlap to some extent (but far from perfectly) with the histological pattern of lung injury referred to as the exudative stage of diffuse alveolar damage (DAD) as is quite commonly reported in ALI/ARDS.

Non-penetrating combat-related thoracic trauma (review)

Combat-related thoracic trauma is a significant cause of morbidity and mortality in all military opera­tions. Penetrating, blunt, and explosive wounds are the most common mechanisms of injury. Visualization diagnosis plays a key role in the treatment. This review discusses the visualization signs of chest injuries from blunt trauma and blast trauma. Objective was to study in detail the mechanisms and visualization signs of non-penetrating combat-related thoracic trauma. 235 literature sources were found in the PubMed system by the query Thoracic AND Trauma AND Combat, 34 of which were selected for further detailed study. In modern warfare, thoracic trauma accounts for 8.6—16.0 % of casualties. Chest X-ray and CT are the visualization methods most commonly used in the evaluation of polytrauma patients from combat and peacetime. Chest X-ray can be quickly obtained in a patient with blunt trauma and emergency conditions that include tension pneumothorax, large hemothorax, chest compression, and others. Chest CT is an important component of trauma visualization. Compared to chest X-ray, chest CT identifies 20 % more pathology, and occult chest trauma due to blunt force trauma can be identified in 71 % of patients. CT provides 38—81 % additional diagnoses compared to chest X-ray.Thoracic trauma is often diagnosed in places of combat. As medical imaging technology moves closer to combat areas, this tool is becoming increasingly available to aid in the diagnosis and rapid treatment of combat-related thoracic trauma. Clinical and surgical management of the traumatized patient relies on skills learned in modern civilian training and honed in war. However, imaging of blunt and explosive injuries may be different in civilian and military settings. The distinct injury pattern and atypical imaging findings of blunt trauma and blast lung injury are important to recognize at an early stage because of the severity of this pathology and the impact of an accurate diagnosis on clinical management.We present our own observations of patients who were treated at the Military Medical Clinical Center of the Northern Region (Kharkiv) in 2022 for non­penetrating combat­related thoracic trauma.

Potential Antifibrotic Effect of Blueberry and Grape Polyphenol Extracts in Acute and Subacute Bleomycin-Induced Lung Tissue Injury Models in Mice

An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Effect of hypofractionated radiotherapy on lung functions in breast cancer patients

Background Adjuvant hypofractionated radiotherapy (RT) used in the management of breast cancer cases, although reduce time and cost, may have serious effects due to the increased dose of radiation. Radiation-induced lung injury is an important side effect of thoracic radiation. Aim In our study, patients assessed by spirometry to detect acute changes in lung functions resulted from radiation exposure during the treatment of breast cancer. Patients and methods In this prospective study, 31 patients with breast cancer, who received adjuvant RT in Ain Shams University Hospitals, were assessed by spirometry before and 8 weeks after the end of RT. Radiation pneumonitis (RP) was graded using the Common Terminology Criteria for Adverse Events, version 5. Pulmonary function was evaluated by spirometry before and 8 weeks after finishing RT to detect changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, forced expiratory flow at 25–75% of FVC (FEF25%–75%), and FEF50% of. Results Five (16.1%) patients developed symptomatic RP. Significant reduction was noticed in FVC and FEV1, while FEV1/FVC ratio, FEF25%–75%, and FEF50% were not significantly affected. It was also observed that FEV1 was sensitive in anticipating RP. Conclusion Spirometry parameters, FEV1 and FVC, significantly decreased after 8 weeks of RT ending, without significant decrease in other parameters, favoring restrictive lung injury pattern. Since most cancer breast patients who developed RP were asymptomatic, spirometry was found to be beneficial in identifying patients with risk of radiation-induced lung injury (RP).

Acute lung injury and recovery in patients with refractory VT/VF cardiac arrest treated with prolonged CPR and veno-arterial extracorporeal membrane oxygenation

AimDescribe the lung injury patterns among patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest (VT/VF OHCA) supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) facilitated resuscitation. MethodsIn this retrospective single-center cohort study including VT/VF OHCA patients supported with VA ECMO, we compared OHCA characteristics, post-arrest computed tomography (CT) scans, ventilator parameters, and other lung-related pathology between survivors, patients who developed brain death, and those with other causes of death. ResultsAmong 138 patients, 48/138 (34.8%) survived, 31/138 (22.4%) developed brain death, and 59/138 (42.7%) died of other causes. Successful extubation was achieved in 39/138 (28%) with a median time to extubation of 8.0 days (6.0, 11.0) in those who survived. Tracheostomy was required in 15/48 (31.3%) survivors. Chest CT obtained on all patients showed lung injury in at least one lung area in 124/135 (91.8%) patients, predominantly in the dependent posterior areas. There was no association between the number of affected areas and survival. Lung compliance was low on admission [26 (19,33) ml/cmH20], improved throughout hospitalization (p = 0.03), and recovered faster in survivors compared to those who died (p < 0.001). VA-ECMO allowed the use of lung-protective ventilation while maintaining normalized PaO2 and PaCO2. Patients treated with V-A ECMO and either IABP or Impella had lower pulmonary compliance and more affected areas on their CT compared to those treated with V-A ECMO alone. ConclusionsLung injury is common among patients with refractory VT/VF OHCA requiring V-A ECMO, but imaging severity is not associated with survival. Reductions in lung compliance accompany post-arrest lung injury while compliance recovery is associated with survival.

The trajectory of COVID-19 cardiopulmonary disease: insights from an autopsy study of community-based, pre-hospital deaths.

BackgroundPost-mortem examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology, however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions.MethodsIn this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy.ResultsThe cohort comprised 22 females and 24 males, median age 64 years (range 19–91) at time of death with illness duration range 0–23 days. Comorbidities associated with poor outcomes in COVID-19 were represented with obesity (BMI>30 kg·m−2) in 19/46 cases (41.3%). Diffuse alveolar damage (DAD) in its early exudative phase was the most common pattern of lung injury, however significant heterogeneity was identified with bronchopneumonia, pulmonary oedema consistent with acute cardiac failure, pulmonary thromboembolism and microthombosis also identified and often in overlapping patterns. Review of clinical records and next of kin accounts suggested a combination of unexpectedly low symptom burden, rapidly progressive disease and psychosocial factors may have contributed to a failure of hospital presentation prior to death.ConclusionsIdentifying such advanced acute lung injury in community-based deaths is extremely unusual and raises the question why some with severe COVID-19 pneumonitis were not hospitalised. Multiple factors that include low symptom burden, rapidly progressive disease trajectories and psychosocial factors provide possible explanations.

CT patterns and serial CT Changes in lung Cancer patients post stereotactic body radiotherapy (SBRT)

BackgroundTo evaluate computed tomography (CT) patterns of post-SBRT lung injury in lung cancer and identify time points of serial CT changes.Materials and methodsOne hundred eighty-three tumors in 170 patients were evaluated on sequential CTs within 29 months (median). Frequencies of post-SBRT CT patterns and time points of initiation and duration were assessed. Duration of increase of primary lesion or surrounding injury without evidence of local recurrence and time to stabilization or local recurrence were evaluated.ResultsPost-SBRT CT patterns could overlap in the same patient and were nodule-like pattern (69%), consolidation with ground glass opacity (GGO) (41%), modified conventional pattern (39%), peribronchial/patchy consolidation (42%), patchy GGO (24%), diffuse consolidation (16%), “orbit sign” (21%), mass-like pattern (19%), scar-like pattern (15%) and diffuse GGO (3%). Patchy GGO started at 4 months post-SBRT. Peribronchial/patchy consolidation and consolidation with GGO started at 4 and 5 months respectively. Diffuse consolidation, diffuse GGO and orbit sign started at 5, 6 and 8 months respectively. Mass-like, modified conventional and scar-like pattern started at 8, 12 and 12 months respectively. Primary lesion (n = 11) or surrounding injury (n = 85) increased up to 13 months. Primary lesion (n = 119) or surrounding injury (n = 115) started to decrease at 4 and 9 months respectively. Time to stabilization was 20 months. The most common CT pattern at stabilization was modified conventional pattern (49%), scar-like pattern (23%) and mass-like pattern (12%). Local recurrence (n = 15) occurred at a median time of 18 months.ConclusionDifferent CT patterns of lung injury post-SBRT appear in predictable time points and have variable but predictable duration. Familiarity with these patterns and timeframes of appearance helps differentiate them from local recurrence.

Immune check-point inhibitor-related pneumonitis: acute lung injury with rapid progression and organising pneumonia with less severe clinical disease.

To improve understanding of the pathology of immune check-point inhibitor (ICI)-related pneumonitis, clinical, radiographic and histopathological features and outcomes were investigated in a cohort of patients who were treatment-naive before receiving ICI inhibition, who underwent lung biopsy, and in whom other potential causes of lung injury were excluded. Patients were retrospectively identified via searches of institutional pathology and clinical records. Patients treated with other modalities for cancer and patients with lung infections or other aetiologies that could cause pneumonitis were excluded. Clinical records were reviewed by pulmonologists. Imaging studies at presentation and follow-up were reviewed by a thoracic radiologist. Pathology was reviewed by thoracic pathologists. Six patients with ICI-related pneumonitis were identified. Two patients presented with respiratory failure requiring mechanical ventilation, diffuse ground glass opacities (GGOs) on chest computed tomography (CT) and acute lung injury (ALI) pattern on transbronchial lung biopsies and had fatal outcomes, despite treatment. The remaining four patients presented with less severe symptoms, predominantly consolidations and patchy ground glass and part solid opacities on chest CT, organising pneumonia (OP) or chronic interstitial inflammation histologically, and showed favourable responses to treatment and remission within months. This study highlights two radiological-pathological patterns of ICI-related pneumonitis with different behaviour: (1) severe respiratory symptoms and diffuse GGOs on imaging correlating with ALI pattern histologically and poor prognosis; and (2) mild respiratory symptoms and consolidations or patchy subsolid opacities on imaging correlating histologically with OP or chronic interstitial inflammation and good outcomes.

Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19.

Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18–92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19–mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.