Autoimmune pulmonary alveolar proteinosis during the treatment of nonspecific interstitial pneumonia complicated by clinically amyopathic dermatomyositis: A case report.

A 46-year-old male was treated with corticosteroids for nonspecific interstitial pneumonia (NSIP). He was referred to our hospital and admitted for worsening dyspnea and diffuse ground-glass opacity on chest computed tomography (CT) during corticosteroid treatment. Gottron's sign was observed, and the patient was diagnosed with clinically amyopathic dermatomyositis on skin biopsy. We increased the corticosteroid dose and added immunosuppressive agents; however, the opacity on the chest CT worsened. Based on periodic-acid-Schiff-positive granular material in the bronchoalveolar lavage fluid and the presence of anti-GM-CSF antibodies, the patient was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP). The concentration of anti-GM-CSF antibodies in preserved serum was also elevated when the patient was diagnosed with NSIP. Thus, we assumed that NSIP and APAP coexisted, and that APAP manifested during immunosuppressive therapy. When exacerbation is observed during the treatment of interstitial pneumonia with immunosuppressive agents, it is necessary to consider APAP.

A Fatal Case of Drug-Induced Lung Injury Potentially Related to Olanzapine.

Drug-induced lung injury (DILI) occurs when exposure to a drug leads to inflammation and, eventually, fibrosis of the lung interstitium. While DILI is a rare side effect of antipsychotic medication, once it manifests, it requires detailed investigation and prompt treatment. Diagnosing DILI can be challenging at times due to its similarity to conditions such as infectious diseases or interstitial pneumonia induced by other causes. We hereby report a fatal case of suspected DILI associated with olanzapine. A 61-year-old female with a history of delusional disorder was admitted to our hospital due to worsened psychiatric symptoms. Ten milligrams of olanzapine had been initiated a week prior to admission by a psychiatrist at the local clinic to control these symptoms. After admission, although the patient claimed no respiratory symptoms, she developed a slight fever and deterioration of chest radiologic findings. Bronchoalveolar lavage revealed a progressively bloody return of fluid, suggesting pulmonary alveolar hemorrhage. Since no respiratory disorders have been noted, and considering the exclusion of other potential diagnoses, DILI was strongly suspected. Although olanzapine was promptly discontinued, the patient's condition rapidly deteriorated. Despite high-dose steroid therapy, the patient's response to treatment was inadequate, and she finally succumbed to the illness. This case highlights that olanzapine may induce lung injury similar to other psychiatric drugs. Furthermore, early diagnosis and treatment are essential for patients with psychiatric disorders who may sometimes present with fewer symptoms.

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review.

Background and Objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease. Methods: For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors". Key Content and Findings: Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC. Conclusions: Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

Mycobacteroides abscessus infection in a patient with tetralogy of Fallot.

A 58-year-old woman with tetralogy of Fallot was referred to our hospital with a 2-month history of hemoptysis and low-grade fever. The sputum smear on admission showed positive results for acid-fast bacilli, and comparative genomic analysis of the cultured sputum confirmed Mycobacteroides abscessus subsp. abscessus infection. Long-term combination antimicrobial therapy gradually improved the patient's symptoms. Although non-tuberculous mycobacteria infection is rarely observed in patients with cyanotic congenital heart disease, a worldwide increase in non-tuberculous mycobacteria infections may increase the incidence of this rare combination.

Reduced Asthma Exacerbations in Adult Patients Treated With Bronchial Thermoplasty.

BACKGROUND: Bronchial thermoplasty (BT) has been shown to be effective in randomized controlled trials of patients with severe asthma who failed to achieve disease control with high-dose inhaled corticosteroids combined with bronchodilators. However, the effectiveness of BT in real-world clinical settings, especially among the Asian population, has not been determined. OBJECTIVE: To evaluate the effectiveness of BT using a nationwide database. METHODS: Using the inpatient and outpatient data from the Japanese Diagnosis Procedure Combination database, we applied a self-controlled case series design to evaluate changes in the composite outcome of hospital admissions and emergency department visits, as well as systemic corticosteroid dose, between 1 year before and after BT. We also conducted subgroup analyses based on patients' profiles. RESULTS: Among the 561 patients with asthma who underwent BT treatment between September 2014 and March 2020, 102 patients with at least 1 outcome were analyzed. Bronchial thermoplasty was significantly associated with an improvement in the composite outcome of hospital admission and emergency department visits (incidence rate ratio 0.53; 95% CI 0.44-0.64). Systemic corticosteroid use was reduced after BT sessions (1931.5 mg [1,341.2-3,725.3 mg] to 641.3 mg [134.2-1,691.1 mg] per person-year; P < .001). Although all groups showed a significant improvement in the composite outcome in the subgroup analyses, BT tended to be less effective among people older than 65 years and those with higher body mass index (>25 kg/m2). CONCLUSIONS: The present study using real-world data suggests that BT may improve asthma control; however, the effectiveness of BT can vary depending on patient baseline profiles.

Clinical characteristics and treatment outcomes of severe asthma patients with a history of multiple biologic drugs use.

BACKGROUND: Asthma control has been shown to improve after clinical use of molecular-targeted biologic drugs. Although most patients have shown favorable responses to biologic drugs, some individuals need to switch to another biologic drug. To date, limited data are available regarding patients who received multiple biologic drugs. OBJECTIVE: We aimed to evaluate the characteristics and outcomes of patients treated with multiple biologic drugs. METHODS: We reviewed severe asthma patients who received biologic drugs between May 2009 and September 2019. Clinical characteristics of patients and changes in annualized asthma exacerbation rates, asthma control test (ACT), and oral corticosteroid (OCS) dose, before and after the use of the final biologic drug, were evaluated. RESULTS: Of the 105 patients who received biologic drugs, 20 patients received multiple biologic drugs. Twelve patients received two biologic drugs, six received three, and two received four. Patients who received multiple biologic drugs tended to have a significantly higher number of allergic or eosinophilic airway comorbidities (allergic rhinitis: p = 0.02, chronic rhinosinusitis with nasal polyps: p < 0.001). Approximately half of the patients changed to different treatments due to uncontrolled comorbidities. Annualized exacerbation rates, ACT, and OCS dose significantly improved after the latest biologic drug use (p = 0.035, p < 0.001, and p = 0.038, respectively). CONCLUSIONS: The results of this study indicated that allergic and eosinophilic airway comorbidities should be considered during the selection of biologic drugs. Furthermore, most patients who received multiple biologic drugs achieved disease control after switching to the optimal biologic drug.

Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture.

BACKGROUND: Primary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages. The conditional reprogramming culture (CRC) method, a combination of a Rho-kinase inhibitor and fibroblast feeder cells, has been applied to cystic fibrosis. The goal of this study was to evaluate the value of CRC in diagnosing PCD in Japanese patients. METHODS: Eleven patients clinically suspected of having PCD were included. Airway epithelial cells were obtained from an endobronchial forceps biopsy and cultured at the air-liquid interface (ALI) combined with CRC. Ciliary movement, ultrastructure, and mutated ciliary protein evaluation were performed using HSVA, TEM, and IF, respectively. Genetic testing was performed on some patients. RESULTS: CRC yielded dense and well-differentiated ciliated cells with a high success rate (∼90%). In patients with PCD, the ciliary ultrastructure phenotype (outer dynein arm defects or normal ultrastructure) and IF findings (absence of the mutated ciliary protein) were confirmed after CRC. In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis. CONCLUSIONS: CRC could be a potential tool for improving diagnostic accuracy and contributing to future clinical and basic research in PCD.

Tryptase and IL-33 in Bronchoalveolar Lavage Fluid May Predict the Types of Eosinophilic Pneumonia and Disease Recurrence.

INTRODUCTION: Eosinophilic pneumonia (EP) is characterized by a marked accumulation of eosinophils in the lungs and blood. Eosinophils and mast cells play an important role in the pathogenesis of EP via release of biomarkers such as tryptase and interleukin (IL)-33. However, the potential role of these biomarkers is not fully understood. OBJECTIVES: We aimed to evaluate the differences among the levels of tryptase and IL-33 in bronchoalveolar lavage fluid (BALF) from several types of EP. We evaluated the differences between the levels of these biomarkers in the recurrent and nonrecurrent cases. METHOD: We prospectively collected the clinical data of patients with EP, diagnosed between 2006 and 2015 in our institution. Bronchoscopy was performed before steroid treatment; BALF was collected. The clinical characteristics of EP patients and the levels of tryptase and IL-33 in BALF were evaluated. RESULTS: We enrolled 15 patients with chronic EP (CEP), 5 with acute EP (AEP), 10 with drug-induced EP, and 6 with angiitis-related EP. Tryptase levels in the CEP group were significantly higher than that in the drug-induced EP group (p = 0.048), while the AEP group had the highest IL-33 levels. Recurrence of EP was noted in 67% of patients with CEP. The levels of tryptase and IL-33 were notably higher in the recurrent cases than that in the nonrecurrent CEP group (p = 0.004, p = 0.04, respectively). Furthermore, there was a positive correlation between the levels of tryptase and IL-33 in the BALF of patients with CEP (ρ = 0.69, p = 0.004). CONCLUSIONS: Tryptase and IL-33 in BALF are useful biomarkers for the assessment of EP types. These biomarkers could be used to predict disease recurrence.

Recurrent spindle cell carcinoma of the lung successfully treated by chemoimmunotherapy.

There is limited evidence for the treatment of sarcomatoid lung carcinoma, especially spindle cell carcinoma (SpCC) because of the rarity of disease. Although the efficacy of combination of chemotherapy and immunotherapy (i.e. chemoimmunotherapy) for non-small cell lung cancer (NSCLC) is well recognized, the effect for SpCC is not fully elucidated. A 72-year-old woman underwent surgical resection for the treatment of stage IIIA SpCC. Recurrence occurred three months after surgery, and then she received combination of carboplatin, paclitaxel, bevacizumab, and atezolizumab. A clinically favourable response was achieved by four cycles of chemoimmunotherapy and sequential maintenance therapy with bevacizumab and atezolizumab. The prognosis of advanced SpCC is generally poor, but chemoimmunotherapy can be a good therapeutic option for the first-line treatment of SpCC.

Characteristics of patients with severe asthma who experienced treatment failure with omalizumab.

BACKGROUND: Omalizumab, an anti-IgE antibody, has been widely used in many countries, including Japan. However, some patients do not respond to omalizumab, and the cause of treatment failure has not been fully elucidated. OBJECTIVE: This study aimed to evaluate the characteristics of adult asthma patients who failed to achieve disease control with omalizumab in a real-world setting. METHODS: We retrospectively reviewed the medical records of patients in Tokyo Women's Medical University Hospital between March 2009 and May 2016. The patient characteristics and factors for treatment failure with omalizumab were evaluated, as were treatment alternatives after discontinuation of omalizumab. RESULTS: In total, 59 patients were included in this study. The omalizumab-ineffective group had a significantly higher number of patients with eosinophilic sinusitis (P = 0.001) and eosinophilic otitis media (P = 0.023) than the omalizumab-effective group. A multivariate analysis revealed that both eosinophilic chronic rhinosinusitis (odds ratio: 23.4; P = 0.011) and eosinophilic otitis media (odds ratio: 6.71; P = 0.039) were associated with treatment failure with omalizumab. Most patients with eosinophilic comorbidities of the ear, nose, and throat (ENT) in the omalizumab-ineffective group received mepolizumab or benralizumab as alternative therapy, following which disease control was achieved. CONCLUSION: Eosinophilic comorbidities of the ENT may affect treatment failure with omalizumab in patients with severe asthma. Anti-interleukin-5 antibody or anti-interleukin-5Rα antibody rather than anti-IgE antibody should be considered as an additional therapy for patients with severe asthma who have eosinophilic comorbidities of the ENT.

Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations.

Multifaceted analysis is recommended for the diagnosis of primary ciliary dyskinesia (PCD). A 31-year-old woman had situs inversus, bronchiectasis, family history of PCD, and compound heterozygous mutations in DNAH5. Her cilia were immotile. Defects in the outer dynein arms were revealed by transmission electron microscopy and loss of DNAH5 proteins in the entire length of axonemes using immunofluorescence (IF). A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure. The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF. IF could be useful to support PCD diagnosis.

A case of pulmonary infarction induced by undiagnosed HIV.

A 25-year-old Chinese man visited our institution due to fever and left chest pain. A chest CT showed infiltrative shadows with pleural effusion. Despite antibiotics treatment, his symptoms gradually worsened. The contrast CT showed deterioration of infiltrative shadows with thromboembolism in pulmonary arteries, suggesting pulmonary infarction. Thereafter, his HIV test turned out to be positive. His symptoms and radiological findings improved after initiation of an anticoagulant therapy. No known risk factors for thromboembolism were identified except HIV infection. The possibility of pulmonary thrombosis should be noted when the HIV patient with acute chest pain and pneumonia-like infiltrative shadow is seen.

Coexistence of diffuse panbronchiolitis and sarcoidosis revealed during splenectomy: a case report.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease caused by CD4+ cell-dominant inflammation. Meanwhile, diffuse panbronchiolitis is a chronic inflammatory respiratory disease predominantly caused by CD8+ lymphocytes and neutrophils. Herein, we report a rare case of sarcoidosis in which the clinical presentation had become evident as diffuse panbronchiolitis after splenectomy for sarcoidosis. CASE PRESENTATION: A 23-year-old Japanese woman was referred to our hospital due to splenomegaly of unknown etiology. Upon admission, chest computed tomography scan revealed centrilobular and randomly distributed small nodules in both lungs. Bronchoalveolar lavage revealed a high proportion of lymphocytes and a decreased CD4/CD8 ratio. However, the biopsy specimens obtained from both the liver and lungs revealed noncaseating epithelioid granulomas, which confirmed the diagnosis of sarcoidosis. The patient underwent splenectomy due to progressive cytopenia and high risk of splenic rupture. After the surgery, the condition of the patient was consistently good for 3 months. Then, she gradually developed productive cough and dyspnea. Both sinus and chest computed tomography scan revealed chronic paranasal sinusitis and deterioration of centrilobular nodules in both lung fields, respectively. The second bronchoalveolar lavage revealed a high proportion of neutrophils, and the bronchoalveolar lavage fluid tested positive for Hemophilus influenzae. The titer of cold agglutinin was elevated, thereby confirming the diagnosis of diffuse panbronchiolitis. On the basis of the clinical and radiological findings, the condition of the patient improved with low-dose macrolide therapy for 3 months. CONCLUSIONS: The coexistence of sarcoidosis and diffuse panbronchiolitis has not been previously reported, and the hidden profiles of diffuse panbronchiolitis may have been revealed by splenectomy.

Activating prostaglandin E2 receptor subtype EP4 increases secreted mucin from airway goblet cells.

Prostaglandin E2 (PGE2) is a ligand of the E-type prostanoid receptors, EP1-4. PGE2 secretion is increased in the airways of patients with asthma by secretory phospholipases A2, which also increases MUC5AC mucin in goblet cells. We hypothesized that PGE2 would also increase MUC5AC mRNA and secreted protein through specific EP receptor activation. We sought to assess the effect of specific EP receptor activation on MUC5AC secretion from ciliated-enriched cells or goblet-enriched cells induced by IL-13. We develop an enriched goblet cell epithelium by growing normal human bronchial epithelial cells at air liquid interface for 14 days in the presence of IL-13. We examined exposure to 4 specific EP receptor agonists at 24 h and 14 days in cells grown with or without IL-13 exposure, and measured MUC5AC mRNA and secreted protein, as well as airway culture morphology, and EP receptor expression. In ciliated-enriched cells grown in the absence of IL-13, the EP4 receptor agonist modestly increased both MUC5AC mRNA and secretion (p < 0.001, 241% increase of transcripts and p < 0.01, 86% increase of secreted protein) but did not visibly change cell morphology. In goblet-enriched cells grown in the presence of IL-13, the EP4 receptor agonist greatly increased both MUC5AC mRNA and protein (p < 0.001, 315% increase of transcripts and 92% increase of secreted protein). Specific activation of the other EP receptor had no effect on secreted mucin. EP4 receptor mRNA and protein were significantly increased in goblet-enriched cells, while the other receptor mRNA were decreased. We conclude that PGE2 stimulates airway mucin production predominantly by EP4 receptor activation in association with increased EP4 receptor expression. This may contribute to mucus hypersecretion as seen in severe asthma.

Tiotropium inhibits mucin production stimulated by neutrophil elastase but not by IL-13.

Tiotropium, a muscarinic antagonist, is approved for the treatment of chronic obstructive pulmonary disease and poorly controlled asthma. Because mucus hypersecretion is characteristic of both of these diseases, and muscarinic agonists stimulate mucus secretion, we hypothesized that tiotropium would attenuate airway MUC5AC expression. We grew normal human bronchial epithelial (NHBE) cells to a goblet cell phenotype with 1 or 5 ng/mL of IL-13 and exposed these cells to 10 nM tiotropium or excipient for the full 14 days. Normally differentiated NHBE cells (without IL-13) were exposed to neutrophil elastase (NE) 1 × 10-7 or 5 × 10-7 M for 1 h. MUC5AC was measured by quantitative PCR and ELISA. Acetylcholine production by the epithelium was evaluated by quantitative PCR and by choline/acetylcholine quantification. Tiotropium had no effect on IL-13-stimulated MUC5AC, but attenuated MUC5AC stimulated by NE (p = 0.007 at 5 × 10-7 M). IL-13 increased CarAT mRNA (p < 0.001 at 5 ng/mL) and acetylcholine concentration in the medium (p = 0.018 at 5 ng/mL), while NE had no effect. Tiotropium had no direct effect on IL-13 or NE-induced CarAT or acetylcholine concentration. Tiotropium decreased MUC5AC stimulated by NE, but had no effect on MUC5AC stimulated by IL-13. These results may be due to IL-13, but not NE, increasing acetylcholine production.

A systematic review of diagnostic methods to differentiate acute lung injury/acute respiratory distress syndrome from cardiogenic pulmonary edema.

BACKGROUND: Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) is often challenging. This systematic review examines studies using biomarkers or images to distinguish ALI/ARDS from CPE. METHODS: Three investigators independently identified studies designed to distinguish ALI/ARDS from CPE in adults. Studies were identified from PubMed, and the Cochrane Central Register of Controlled Trials database until July 3, 2017. RESULTS: Of 475 titles and abstracts screened, 38 full texts were selected for review, and we finally included 24 studies in this systematic review: 21 prospective observational studies, two retrospective observational studies, and one retrospective combined with prospective study. These studies compared various biomarkers to differentiate subjects with ALI/ARDS and in those with CPE, and 13 calculated the area under the receiver operator characteristic curve (AUC). The most commonly studied biomarker (four studies) was brain natriuretic peptide (BNP) and the discriminatory ability ranged from AUC 0.67-0.87 but the timing of measurement varied. Other potential biomarkers or tools have been reported, but only as single studies. CONCLUSIONS: There were no identified biomarkers or tools with high-quality evidence for differentiating ALI/ARDS from CPE. Combining clinical criteria with validated biomarkers may improve the predictive accuracy.

Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC.

BACKGROUND AND OBJECTIVE: Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells. METHODS: Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production. We examined MUC5AC secretion from NHBE cells exposed to recombinant human (rh) periostin or IL-13 in the presence and absence of OC-20, a periostin-neutralizing antibody. RESULTS: IL-13 induced periostin protein which was predominantly secreted towards the basal surface of the cells. Periostin production was much greater from goblet cells than ciliated cells (P < 0.001). Periostin production after exposure to IL-13 was attenuated by both leflunomide (P < 0.001) and PD98059 (P < 0.001). The addition of exogenous periostin modestly increased MUC5AC secretion (P < 0.01), but did not visibly change cell morphology. IL-13-induced MUC5AC secretion was attenuated by OC-20 (P < 0.01). CONCLUSION: Periostin production in differentiated airway cells is mediated by JAK/STAT6 and MEK/ERK pathways. Periostin secretion is much greater from immunologically active goblet cells. IL-13-driven mucin production is partially inhibited by OC-20.

Prognostic implications of aspiration pneumonia in patients with community acquired pneumonia: A systematic review with meta-analysis.

Aspiration pneumonia is thought to be associated with a poor outcome in patients with community acquired pneumonia (CAP). However, there has been no systematic review regarding the impact of aspiration pneumonia on the outcomes in patients with CAP. This review was conducted using the MOOSE guidelines: Patients: patients defined CAP. EXPOSURE: aspiration pneumonia defined as pneumonia in patients who have aspiration risk. Comparison: confirmed pneumonia in patients who were not considered to be at high risk for oral aspiration. OUTCOMES: mortality, hospital readmission or recurrent pneumonia. Three investigators independently identified published cohort studies from PubMed, CENTRAL database, and EMBASE. Nineteen studies were included for this systematic review. Aspiration pneumonia increased in-hospital mortality (relative risk, 3.62; 95% CI, 2.65-4.96; P < 0.001, seven studies) and 30-day mortality (3.57; 2.18-5.86; P < 0.001, five studies). In contrast, aspiration pneumonia was associated with decreased ICU mortality (relative risk, 0.40; 95% CI, 0.26-0.60; P < 0.00001, four studies). Although there are insufficient data to perform a meta-analysis on long-term mortality, recurrent pneumonia, and hospital readmission, the few reported studies suggest that aspiration pneumonia is also associated with these poor outcomes. In conclusion, aspiration pneumonia was associated with both higher in-hospital and 30-day mortality in patients with CAP outside ICU settings.