新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice

RATIONALE AND OBJECTIVE: The acute respiratory distress syndrome (ARDS) caused by avian influenza H5N1 viral infection has been reported in many humans since this virus was found to infect humans in Hong Kong in 1997, but no studies regarding an animal model of ARDS with H5N1 viral infection have been found in the literature. Here we present a mouse model of ARDS induced by H5N1 virus. METHODS: Six- to 8-wk-old BALB/c mice were inoculated intranasally (50 micro l) with 1 x 10(2) 50% mouse infectious doses of A/Chicken/Hebei/108/2002 (H5N1) virus. Lung injury was assessed by observation of lung water content and histopathology. Arterial blood gas, white blood cell count in bronchial alveolar lavage fluid, and tumor necrosis factor-alpha and interleukin-6 in bronchoalveolar lavage fluid and serum were measured at the indicated time points. RESULTS: Our data showed that H5N1 viral infection in mice resulted in typical ARDS, which was characterized by the following features: (1) about 80% of mice (13 of 16) dead on Days 6 to 8 postinoculation; (2) highly edematous lungs and dramatically increased lung wet:dry weight ratios and lung wet weight:body weight ratios; (3) inflammatory cellular infiltration, alveolar and interstitial edema, and hemorrhage in lungs; (4) progressive and severe hypoxemia; and (5) significant increase in neutrophils, tumor necrosis factor-alpha, and interleukin-6 in BALF. CONCLUSION: These results suggested that we successfully established a mouse model of ARDS with H5N1 viral infection, which may benefit further investigation into the pathogenesis of human ARDS induced by H5N1 virus.     

Newly recognized causes of acute lung injury: transfusion of blood products, severe acute respiratory syndrome, and avian influenza

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical syndrome that has an ever-growing list of potential causes. The transfusion of blood products is often a life-saving therapy, but it can be associated with the development of ALI/ARDS. Transfusion-related ALI is now the leading cause of transfusion-associated fatalities in the United States. Two infectious causes of ALI/ARDS, severe acute respiratory syndrome and H5N1 influenza, have recently emerged and have the potential for pandemic spread. This article discusses the clinical importance, pathogenesis, diagnosis, management, and prevention of these newly recognized causes of respiratory failure.     

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.Acute lung injury is a continuum of clinical and radiographic changes, terminating at its most severe, with acute respiratory distress syndrome. Infection with highly pathogenic avian influenza (HPAI) viruses of the H5N1 and more recent H7N9 subtypes often leads to acute lung injury whereas seasonal influenza viruses and the 2009 pandemic H1N1 influenza viruses do so more rarely. The underlying mechanisms of influenza-related acute lung injury remain unclear, and effective therapies are lacking. Viruses that are highly pathogenic to humans (e.g., H5N1 viruses) may differ intrinsically from the less pathogenic (LP) (e.g., seasonal H1N1) viruses in their replication competence, cell tropism, and/or cytokine dysregulation (1, 2). Early treatment of H5N1 disease with the antiinfluenza drug oseltamivir is helpful but does not ensure a favorable outcome (3). Thus, effective adjunctive therapies that do not compromise beneficial host defenses are needed (4).H5N1 (5) and H7N9 (6) influenza viruses target alveolar epithelial cells, which form the crucial gas exchange interface in the lung. These cells also help to maintain intraalveolar and intravascular fluid homeostasis by vectorial transport of sodium, chloride, and water from the apical to the basolateral surface of the alveolar epithelium [alveolar fluid clearance (AFC)]. Impaired AFC and increased alveolar protein permeability (APP) contribute to acute lung injury (7). Therapies that normalize alveolar fluid clearance are likely to be free of off-target effects, unlike immunomodulation, that may promote virus replication.Human bone marrow-derived multipotent mesenchymal stromal cells (MSCs) have applications in multiple clinical disorders, including sepsis, myocardial infarction, diabetes, and acute renal failure (8). Allogeneic MSC therapy has beneficial preclinical effects on endotoxin-, bacteria-, and ventilator-induced acute lung injury (9) via MSC secretion of the soluble paracrine growth factors angiopoietin-1 (Ang1) and keratinocyte growth factor (KGF) (9, 10). MSCs can also transfer mitochondria and microvesicles that modulate immunity and epithelial response to injury (11). Current clinical trials are testing MSCs as a therapy for sepsis and acute respiratory distress syndrome (12). However, little is known about the impact of MSCs on acute respiratory viral infections, including influenza, with the exception of a study in which MSCs failed to reduce influenza-induced lung injury in mice (13). Here, we showed that influenza A/H5N1 virus infection dysregulates AFC and APP in vitro by inducing infected cells to release soluble mediators that down-regulate alveolar sodium and chloride transporters. When we cocultured alveolar epithelium with MSCs, these injury mechanisms were prevented or reduced. We then treated mice infected with influenza A/H5N1 with MSCs and demonstrated a clinically significant reduction in lung pathology and increased survival in association with a modulation of these pathogenic mechanisms in vivo.     

Influenza heute und in Zukunft

Every year, influenza causes seasonal epidemics and is responsible for increased morbidity and mortality worldwide. In general, clinical signs include fever, respiratory symptoms and myalgia. Human influenza viruses include influenza viruses A/H1N1, A/H3N2, A/H1N1pdm09, influenza virus B and influenza virus C. Wild waterfowl are the natural reservoir of influenza A virus. On a sporadic basis novel viruses can emerge from the zoonotic reservoir and cross the species barrier. In such events clinical presentation in humans can range from mild (e.g. conjunctivitis) to severe pneumonia and acute respiratory distress syndrome (ARDS). In early 2013, a novel avian influenza A virus H7N9 emerged in China and the clinical presentation included bilateral pneumonia with ARDS and a high case fatality rate. In this article a summary is given on diagnosis, therapy and prophylaxis of influenza and on future developments.     

山西省首例高致病性禽流感A/H5N1病毒感染患者的救治体会

目的 探索高致病性禽流感A/H5N1病毒感染(简称人禽流感)病例的临床特点及治疗体会.方法 对2009年1月17口山西省太原市第四人民医院收治的1例人禽流感患者的临床表现、实验室检查、影像学改变及治疗方法等进行总结.结果 患者鼻咽抽取物A/H5N1病毒经逆转录聚合酶链反应(RT-PCR)、实时PCR榆测A/H5N1病毒核酸阳性,确诊为人禽流感病例.患儿女,2岁11个月,体重11 kg.患儿平素体健,发病的有活禽屠宰市场环境暴露史.以发热、咳嗽、呼吸困难为主要症状;肺部病灶进展快,病程第8天肺部病变迅速进展,x线胸片呈"白肺",病情迅速进展为ARDS,静脉应用甲泼尼龙165 mg(15 mg·kg-1·d-1)及无创通气治疗,病程第9天病情有所好转,肺部病灶明显吸收;病程第11天开始给予奥司他韦及100 ml高滴度A/H5N1病毒疫苗免疫血浆,后患者病情日见好转,氧合指数及各种酶学指标恢复正常,肺内病灶明显吸收;病程第28大患者好转出院.结论 人禽流感发现晚、病情重、进展快,临床主要表现为严重的ARDS;有效的氧疗及呼吸支持是治疗的基础;糖皮质激素对肺部病灶的吸收有一定疗效,使用剂量有待进一步探讨;A/H5N1病毒疫苗免疫血浆治疗可能对改善患者的预后有一定帮助.     

Acute Respiratory Distress Syndrome as a presenting manifestation in young patients infected with H1N1 influenza virus

Introduction

The new strain of influenza A (H1N1) 2009, often referred to colloquially as “swine flu”, which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people.

Patients

In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support.

Results

Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support.

Conclusions

The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people.     

Oxygen free radical involvement in acute lung injury induced by H5N1 virus in mice

Background

Acute lung injury is an important cause of death in humans infected with H5N1. It has been found that oxygen free radicals (OFRs) are elevated in lung tissue during influenza virus infections. In this study, we used a mouse model to explore the role of OFRs in acute lung injury caused by H5N1 viral infection.

Methods

Four‐ to six‐week‐old male specific pathogen‐free BALB/c mice were inoculated intranasally with 10⁵ 50% tissue culture infective doses (TCID₅₀) of highly pathogenic A/Chicken/Hebei/108/2002 (H5N1) viruses and were then given 1000 IU of lauric acid modified superoxide dismutase (LA‐SOD) by intraperitoneal injection, starting 2 days post‐infection and continuing for 6 days.

Results

The extent of lung injury and the concentration of OFRs were higher, and the SOD activity was lower in H5N1 virus‐infected mice than that in uninfected control mice on days 3, 6, and 7 post‐inoculation. Weak amelioration of clinical signs, a minor decrease in the total mortality and the extent of lung injury, and the lower OFRs concentration were seen in the LA‐SOD treatment group, but a reduction in lung virus titers was not observed in the LA‐SOD treatment at all time points.

Conclusions

The LA‐SOD treatment has a mild inhibitory effect on H5N1 influenza virus infection in mice. OFRs, therefore, might play an important role in the pathogenesis of acute lung injury induced by H5N1 virus.     

Influenza A (H1N1) virus‐induced hepatocellular injury in a kidney transplant patient

M. Daudé, J.M. Mansuy, J. Guitard, G. Basse, L. Esposito, J. Izopet, L. Rostaing, N. Kamar. Influenza A (H1N1) virus‐induced hepatocellular injury in a kidney transplant patient.
Transpl Infect Dis 2011: 13: 70–72. All rights reserved. Abstract: The swine‐origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus‐induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.     

Surveillance of hospitalised severe cases of influenza A(H1N1)pdm09 and related fatalities in nine EU countries in 2010–2011

Please cite this paper as: Snacken et al. (2012) Surveillance of hospitalised severe cases of Influenza A(H1N1)pdm09 and related fatalities in nine EU countries in 2010–2011. Influenza and Other Respiratory Viruses 6(601), e93–e96. A few months into the 2009 influenza pandemic, nine European countries implemented case‐based surveillance of hospitalised severe influenza infections. In the present study, we assess the association between patient characteristics, in particular underlying conditions, and the severity level of influenza A(H1N1)pdm09 infection during the 2010‐2011 season. Patient age, the presence of underlying conditions, pneumonia, acute respiratory distress syndrome (ARDS) and the need for ventilation were significantly associated with the severity of influenza A(H1N1)pdm09 infection. Despite limitations essentially because of the heterogeneity of the data reported, this study provides insight into severe influenza cases.     

Report of the 'mechanisms of lung injury and immunomodulator interventions in influenza' workshop, 21 March 2010, Ventura, California, USA

The clinical course of influenza and the extent of lung injury are determined by both viral and host factors, as well as sometimes secondary bacterial infections and exacerbations of underlying conditions. The balance between viral replication and the host immune responses is central to disease pathogenesis, and the extent of lung injury in severe influenza infections may be due in part to overly exuberant or dysregulated innate inflammatory responses or sometimes deficient responses. Acute respiratory distress syndrome (ARDS) is the principal cause of respiratory failure associated with severe influenza. ARDS can be triggered by both direct lung insults (e.g. respiratory pathogens) and systemic insults (e.g. sepsis), and the lung damage is exacerbated by the inflammatory response associated with either infectious or non-infectious insults. This workshop aimed to review the current understanding of lung injury in acute influenza and describe cellular and molecular mechanisms of lung injury that are common to influenza and infections by other respiratory pathogens. In addition, therapeutic agents that target host response proteins and pathways were identified and investigational agents in development reviewed. A logical strategy would be to combine antiviral treatment with drugs that modify excessive host responses or supplement deficient ones. However, a better understanding of common cell signalling pathways associated with acute lung injury caused by influenza and other pathogens is necessary to understand immunopathologic causes of lung injury. This will help determine which immunomodulatory interventions might be useful, and to predict the appropriate timing and consequences of their use.     

Recovery of pulmonary functions,exercise capacity,and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis

Background

Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge.

Objectives

The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011.

Patients and Methods

Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL_CO), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ).

Results

Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), DL_CO, and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge.

Conclusion

The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.     

A case of successful treatment with polymyxin B-immobilized fiber column direct hemoperfusion in acute respiratory distress syndrome after influenza A infection

We report a case of acute respiratory distress syndrome (ARDS) after influenza A infection who was successfully treated with combined treatment including direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) column. A 56-year-old Japanese man was admitted to our hospital in January 2010 because of progressive dyspnea, hypoxemia, fever and bilateral diffuse infiltration on chest radiograph after pandemic influenza A infection. His chest computed tomography showed diffuse and patchy bilateral ground-glass opacities, and we diagnosed ARDS after influenza A infection. The patient was successfully treated with PMX-DHP in addition to the treatment with oseltamivir, corticosteroid, sivelestat and antibiotics with mechanical ventilation, and the patient recovered with only minor pulmonary fibrotic change. Although the efficacy of PMX-DHP treatment in patients with acute lung injury (ALI)/ARDS after influenza virus infection is not well established, this treatment could be a possible therapeutic modality in treating the patients with this disease.     

湖南省高致病性人禽流行性感冒一例临床分析

目的 了解高致病性H5N1人禽流行性感冒(流感)病例的临床表现、实验室检查、影像学特征、治疗及其预后.方法 对2009年1月在湖南省怀化市第一人民医院收治的1例高致病性H5N1人禽流感的临床表现、实验室检查、影像学改变和治疗等多方面的资料进行回顾总结.结果 患者经RT-PCR、实时荧光定量PCR方法确诊为高致病性H5N1人禽流感病例.患者发病前有禽流感环境暴露史,以咳嗽、咳痰起病,继而出现高热、咯血,病情进行性加重,出现呼吸困难,伴外周血WBC和淋巴细胞明显降低,肝功能和心肌酶谱明显异常.发病第6天胸部影像学可见右肺实变,继而迅速扩展至双肺,出现急性呼吸窘迫综合征(ARDS)样肺部表现.经抗病毒、抗细菌、精皮质激素、呼吸机支持和对症治疗未见好转,于发病后第12天死于多器官功能衰竭.结论 高致病性H5N1人禽流感病变进展快,出现ARDS合并多器官功能损害时,预后不佳.     

安徽省阜阳市首例H5N1型人禽流感临床报告

目的了解人感染高致病性H5N1型禽流感流行病学和临床学特征及防治手段。方法对本院收治的1例人感染高致病性H5N1型禽流感病例的相关资料进行回顾性分析。结果患者为26岁年轻孕妇,有病、死家禽接触史,临床表现为以急性呼吸窘迫综合征为主的全身多器官功能障碍,治疗上采取了以机械通气为主的综合性措施,治愈出院。结果提高对人感染高致病性H5N1型禽流感诊断的警惕性,及早干预是降低病死率的关键环节。     

Acute exacerbation of idiopathic pulmonary fibrosis after pandemic influenza A (H1N1) vaccination

We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.     

Influenza A H1N1 induces declines in alveolar gas exchange in mice consistent with rapid post‐infection progression from acute lung injury to ARDS

Background Patients with severe seasonal or pandemic influenza pneumonia frequently develop acute respiratory distress syndrome (ARDS). One clinical diagnostic criterion for ARDS is the P_aO₂:F_iO₂ ratio, which is an index of alveolar gas exchange. However, effects of H1N1 influenza infection on P_aO₂:F_iO₂ ratios and related pathophysiologic readouts of lung function have not been reported in mice. Methods To develop a method for determining P_aO₂:F_iO₂ ratios, uninfected mice were anesthetized with pentobarbital, diazepam/ketamine, or inhaled isoflurane. Subsequently, they were allowed to breathe spontaneously or were mechanically ventilated. After 15 minutes exposure to room air (F_iO₂ = 0·21) or 100% O₂ (F_iO₂ = 1·0), carotid P_aO₂ was measured. To determine influenza effects on P_aO₂:F_iO₂, mice were challenged with 10 000 p.f..u./mouse influenza A/WSN/33. Results P_aO₂:F_iO₂ ratios were abnormally low (≤400 mmHg) in spontaneously breathing mice. Mechanical ventilation with positive end‐expiratory pressure was required to obtain P_aO₂:F_iO₂ ratios in uninfected mice consistent with normal values in humans (≥600 mmHg). At day 2 following infection P_aO₂:F_iO₂ ratios indicated the onset of acute lung injury. By day 6, P_aO₂:F_iO₂ ratios were <200 mmHg, indicating progression to ARDS. Impaired gas exchange in influenza‐infected mice was accompanied by progressive hemoglobin desaturation, hypercapnia, uncompensated respiratory acidosis, hyperkalemia, and polycythemia. Conclusions Influenza infection of mice results in impairment of alveolar gas exchange consistent with rapid development of acute lung injury and progression to ARDS. P_aO₂:F_iO₂ ratios may be of utility as clinically relevant and predictive outcome measures in influenza pathogenesis and treatment studies that use mouse models.