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Obesity leads to an increase in the incidence and severity of asthma. Adipokines, such as leptin, secreted by adipocytes induce systemic inflammation, causing airway inflammation. We previously reported that leptin activates both inflammatory and structural cells, including lung fibroblasts. However, little is known about the differential leptin expression and responsiveness to leptin in asthmatic individuals and healthy controls (HC). In this study, we investigated the expression and origin of leptin in asthmatic airways. We also compared the effect of leptin on asthmatic and HC fibroblasts.Lung specimens from asthmatic and non-asthmatic patients were analyzed by immunohistochemical staining using anti-leptin and anti-CD163 antibodies. Leptin mRNA and protein levels in human monocytes were detected by real-time PCR and western blotting and ELISA, respectively. We used flow cytometry to analyze asthmatic and HC lung fibroblasts for leptin receptor (Ob-R) expression. Further, we determined cytokine levels using cytometric bead array and ELISA and intracellular phosphorylation of specific signaling molecules using western blotting.Asthma specimens displayed accumulation of leptin-positive inflammatory cells, which were also positive for CD163, a high-affinity scavenger receptor expressed by monocytes and macrophages. Leptin expression was observed at both transcript and protein levels in human blood-derived monocytes. No significant differences were observed between asthmatic and HC lung fibroblasts in Ob-R expression, cytokine production, and intracellular phosphorylation of p38 mitogen-activated protein kinase.Our findings reveal similar responsiveness of control and asthmatic fibroblasts to leptin. However, the accumulation of inflammatory leptin-producing monocytes in the airway may contribute to the pathogenesis of asthma.

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

This manual has been compiled by a joint production committee with the Diffuse Lung Disease Assembly of the Japanese Respiratory Society (JRS) to provide a practical manual for the epidemiology, diagnosis, and treatment of intractable diffuse pulmonary diseases. The contents are based upon the results of research into these diseases by the Diffuse Pulmonary Diseases Study Group (principal researcher: Sakae Homma) supported by the FY2014-FY2016 Health and Labor Sciences Research Grant on Intractable Diseases. This manual focuses on: 1) pulmonary alveolar microlithiasis, 2) bronchiolitis obliterans, and 3) Hermansky-Pudlak Syndrome with interstitial pneumonia. As these are rare/intractable diffuse lung diseases (2 and 3 were first recognized as specified intractable diseases in 2015), there have not been sufficient epidemiological studies made, and there has been little progress in formulating diagnostic criteria and severity scales; however, the results of Japan's first surveys and research into such details are presented herein. In addition, the manual provides treatment guidance and actual cases for each disease, aiming to assist in the establishment of future modalities. The manual was produced with the goal of enabling clinicians specialized in respiratory apparatus to handle these diseases in clinical settings and of further advancing future research and treatment.

BackgroundDiffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.MethodsWe conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.ResultsTwenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted )) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted ConclusionsIDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Fibroblasts provide a structural framework for multiple organs, and are essential for wound repair and fibrotic processes. Here, we demonstrate functional roles of forkhead box L1 (FOXL1), a transc...

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients’ serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P Lay summary High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2, has become a global pandemic. Many survivors of serious COVID‐19 pneumonia have long‐term residual pulmonary disease. However, there is little documentation of the histopathological characteristics of lung sequelae post‐COVID‐19 and effective treatments. We present two Japanese cases of lung sequelae post‐COVID‐19. The patients were histopathologically diagnosed with organizing pneumonia (OP) or OP with fibrosis and no diffuse alveolar damage on video‐assisted thoracoscopic surgery. Case 1, who had been diagnosed with OP, was successfully treated with corticosteroid and other immunosuppressive agents over a 6‐month period. Although case 2, who had been diagnosed with OP with fibrosis, had a partial and unsatisfactory response to immunosuppressive agents, the patient responded to antifibrotic treatment including nintedanib., We present two Japanese cases of lung sequelae post coronavirus disease 2019 (COVID‐19). The patients were histopathologically diagnosed with organizing pneumonia (OP) or OP with fibrosis and no diffuse alveolar damage on video‐assisted thoracoscopic surgery. Case 1, who was diagnosed with OP, was successfully treated with corticosteroid and other immunosuppressive agents over a 6‐month period. Although case 2, who was diagnosed with OP with fibrosis, had a partial and unsatisfactory response to immunosuppressive agents, the patient responded to antifibrotic treatment including nintedanib.

A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved.

Objective Intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) frequently present with similar clinical, endoscopic and pathological features, therefore it is difficult to differentiate between them. The aim of this study was to elucidate the diagnostic delay and prognosis of ITB cases, initially misdiagnosed as IBD. Methods ITB cases were selected from the hospitalized patient list between April 2004 and March 2017 in a tuberculosis center in Japan. We retrospectively evaluated the initial diagnosis, clinical characteristics, endoscopic and pathological findings, bacterial examinations, treatment and prognosis. Results Among 66 ITB patients, ten patients were initially misdiagnosed as IBD. Seven patients were male and the median age was 60.5 years (23-74 years). After the diagnosis of IBD, all the patients were treated with mesalazine, in addition to corticosteroids in two patients and sequential azathioprine and infliximab in one. The median duration of diagnostic delay was 5.5 months (range 0.5-17 months). Eight patients had active pulmonary tuberculosis at the diagnosis of ITB. Acid-fast bacilli were confirmed in four of seven patients by reevaluation of the pathological specimens at the IBD diagnosis. Two patients needed intestinal resection and one with erroneous corticosteroid use for IBD died due to respiratory failure in spite of receiving appropriate treatment for tuberculosis. Conclusion ITB patients were frequently misdiagnosed and treated as IBD, thus resulting in a poor clinical outcome even after finally making a correct diagnosis and administering appropriate treatment. On diagnosis of IBD and/or treatment failure, chest radiograph and acid-fast bacilli of the pathological specimens should be carefully evaluated in order to rule out tuberculosis.

Bacterial catalase is important for intracellular survival of the bacteria. This protein of Propionibacterium acnes, one of possible causes of sarcoidosis, induces hypersensitive Th1 immune responses in sarcoidosis patients. We examined catalase expression in cultured P. acnes isolated from 19 sarcoid and 18 control lymph nodes and immunohistochemical localization of the protein in lymph nodes from 43 sarcoidosis and 102 control patients using a novel P. acnes-specific antibody (PAC) that reacts with the catalase protein, together with the previously reported P. acnes-specific PAB and TIG antibodies. High catalase expression of P. acnes cells was found during stationary phase in more isolates from sarcoid than from non-sarcoid lymph nodes and was associated with bacterial survival under H2O2-induced oxidative stress. In many sarcoid and some control lymph nodes, catalase expression was detected at the outer margins of PAB-reactive Hamazaki-Wesenberg (HW) bodies in sinus macrophages, the same location as catalase expression on the surface of cultured P. acnes and the same distribution as bacterial cell membrane-bound lipoteichoic acid in HW bodies. Some or no catalase expression was detected in sarcoid granulomas with PAB reactivity or in clustered paracortical macrophages packed with many PAB-reactive small-round bodies. HW bodies expressing catalase may be persistent P. acnes in sinus macrophages whereas PAB-reactive small-round bodies with undetectable catalase may be activated P. acnes proliferating in paracortical macrophages. Intracellular proliferation of P. acnes in paracortical macrophages may lead to granuloma formation by this commensal bacterium in sarcoidosis patients with Th1 hypersensitivity to certain P. acnes antigens, including catalase.

Immunoglobulin G4-related disease is a systemic disease characterised by tumefactive lesions with abundant IgG4-positive plasma cells and elevated serum IgG4 concentrations [1–4]. We previously assessed IgG4-related respiratory disease (IgG4-RRD) with extrathoracic manifestations [5]. IgG4-RRD develops through the lymphatic routes in the lungs and responds well to corticosteroid therapy with a benign prognosis [5–7]. However, whether interstitial pneumonia (IP) with IgG4-positive plasma cell infiltration in the lungs without the extrathoracic lesions of IgG4-related disease could be considered a type of IgG4-RRD is controversial., This study suggests that IgG4+ IP with abundant IgG4+ cells and elevated serum IgG4 levels could be treated differently from IgG4-related respiratory disease due to potential differences in disease behaviour and response to corticosteroid therapy https://bit.ly/3dUo2cu

Yellow nail syndrome (YNS) is a rare entity characterized by thickened yellowish nails, lymphedema and respiratory manifestations such as pleural effusion. Lymphatic dysfunction is considered as a cause of YNS. However, evidence of systemic dilatation/hyperplasia of lymphatics based on autopsy in YNS is not available. In this report, autopsy revealed dilatation and hyperplasia of lymphatic vessels in lungs, visceral and parietal pleurae, and intestines. We identified the direct opening of lymphatic vessels of the visceral pleura to the pleural cavity, which indicated the pathophysiology of uncontrollable pleural effusion in YNS. The current case was compromised with primary biliary cholangitis (PBC). The onset of PBC seemed to be related with the progression of YNS.

A 71‐year‐old non‐smoker woman was admitted to our hospital complaining of a six‐month history of dry cough. She had kept java sparrow for nine years and has been raising budgerigars for the previous eight months. High‐resolution computed tomography (HRCT) images of the chest revealed reticulonodular lesions predominantly in the bilateral upper lobes. Surgical lung biopsy specimens showed non‐caseous epithelioid cell granulomas in the alveolar spaces, including irregular and centrilobular fibrosis with pleuroparenchymal fibroelastosis. When she started using a duck feather duvet at home, she developed dyspnoea and chest HRCT abnormalities progressively deteriorated. The results of precipitation of antibodies against duck feather, java sparrow, and budgerigars dropping extracts were positive in sera. Consequently, the patient was diagnosed as having chronic bird fancier's lung with acute exacerbation caused by the use of a feather duvet. After combination treatments with corticosteroid and cyclosporine, her respiratory symptoms and reticulonodular shadow immediately improved., This is a case of chronic bird fancier's lung (BFL) (java sparrow and budgerigars) presenting with acute exacerbation due to exposure to feather duvet. Chronic BFL occasionally can associate with pleuroparenchymal fibroelastosis (PPFE). Searching for precipitins against antigens of bird droppings and feather is useful for our clinicians to make a diagnosis of BFL.

A 63-year-old woman with pulmonary adenocarcinoma (stage IIIB) that was positive for an epidermal growth factor receptor (EGFR) mutation and an anaplastic lymphoma kinase (ALK) rearrangement was treated with erlotinib as the first-line treatment, resulting in a stable disease. Due to skin rashes, fatigue and anorexia, erlotinib was suspended on erlotinib day 44. Alectinib was administered as the second-line treatment, exhibiting a partial response. On alectinib day 56, drug-induced lung injury forced suspension of alectinib, which was cured with corticosteroid therapy. ALK-tyrosine kinase inhibitors may be more effective for patients positive for both EGFR mutation and ALK rearrangement than other agents.

A 56-year-old woman presented to our hospital with a 4-month history of worsening chest pain. She denied having any respiratory symptoms, such as dyspnea, sputum, cough, or hemoptysis, or any history of smoking or exposure to dusts. One year previously she had a vertebral fracture. There was no specific family history, including pulmonary or autoimmune diseases. Chest CT performed 3 years earlier showed multiple thin-walled pulmonary cysts, although no further investigations were performed.

Background: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. Objectives: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. Methods: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. Results: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2–4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. Conclusions: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis.

Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. Methods In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus , and 2) bronchiectasis or mucoid impaction in the central bronchi. Results Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44–68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE ( Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. Conclusions This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β- d -glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA.

A 58-year-old woman was referred to our hospital with a chief complaint of exertional dyspnea. Bronchoscopy failed to establish a diagnosis, and the patient subsequently died suddenly due to respiratory insufficiency because of advanced pulmonary hypertension (PH). The pathological diagnosis at autopsy was pulmonary veno-occlusive disease (PVOD). PVOD is difficult to diagnose antemortem and has a poor prognosis. Lung transplantation is the only curative treatment for PVOD.

Background The diagnosis of chronic hypersensitivity pneumonitis (CHP) is often based on the pathology, but evidence is scarce that a pathological diagnosis of CHP may mislead the multidisciplinary diagnosis. Method We enrolled patients from the consultation case archive whose pathological findings were suggestive of CHP but had a multidisciplinary diagnosis of non-CHP. The histopathological slides were sent to another pathologist, and the ones confirmed with CHP were sent for an additional multidisciplinary discussion (MDD). We examined clinicopathological features of the cases confirmed to be non-CHP through MDD. Results Among the 243 cases, five were diagnosed as non-CHP through an additional MDD. The most common causes of discrepancy were the presence of strong autoimmune features, a low lymphocyte level in the bronchoalveolar lavage fluid, and a lack of nodular shadow or mosaic attenuation on computed tomography. Conclusions Cases of suspected CHP on pathology may be determined to be non-CHP through MDD.

SummarySecretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-β and IL-8.

Active tuberculosis is an important complication in Japanese lung cancer patients. We studied the generation-wise trend of latent tuberculosis infection (LTBI) among lung cancer patients. We analyzed background data including birth year, lung cancer status, and interferon-gamma release assay (IGRA) data of lung cancer patients who were admitted to National Hospital Organization Tokyo National Hospital from 2010 to 2016. Of the 1450 cases, 7 showed active tuberculosis and 45 had previous tuberculosis. Of the remaining 1398 patients, 795 underwent IGRAs and 120 (15%) of them were found to have LTBI. Patients with LTBI were older (p = 0.0005), and the proportion of smokers was also higher in this group (p = 0.0159) than among those without LTBI. LTBI incidence decreased from 33% among patients born in the 1920s to 21%, 15%, 9.8%, and 5.1% among those born in the 1930s, 1940s, 1950s, and after 1960, respectively. A significant decrease in the smoking adjusted risk ratio was also observed with every generation (p 0.0001). Our study suggests that the total number of patients with active tuberculosis comorbid with lung cancer will greatly decrease in the future in Japan. However, owing to recent improvements in lung cancer prognosis due to advances in cancer medication, careful monitoring for active tuberculosis development may be required in lung cancer patients with LTBI.

Background There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. Objective This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. Methods Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. Results The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. Conclusions The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Background Epithelial-mesenchymal transition (EMT) is reported to promote airway remodeling in asthmatics, which is the main histological change that causes complex and severe symptoms in asthmatics. However, little is known about whether EMT also plays a role in acute exacerbations of asthma evoked by respiratory tract infections. Methods A human lung adenocarcinoma line, A549, was incubated with TGF-β1 at 10 ng/ml to induce EMT. Then the cells were stimulated with CpG ODN. Expression of surface and intracellular molecules was analyzed by flow cytometry. IL-6, IL-8 and MCP-1 in the culture supernatant were measured by Cytometric Bead Assay, and the expression of mRNA was quantitated by real-time PCR. CpG ODN uptake was analyzed by flow cytometry. Results The culture supernatant levels of IL-6, IL-8 and MCP-1 and the expression of mRNA for these cytokines in CpG ODN-stimulated A549 cells that had undergone EMT was significantly higher compared to those that had not. Addition of ODN H154, a TLR9-inhibiting DNA, significantly suppressed the CpG ODN-induced production of those cytokines. However, flow cytometry found the level of TLR9 expression to be slightly lower in A549 cells that had undergone EMT compared to those that had not. On the other hand, CpG ODN uptake was increased in cells that had undergone EMT. Conclusions EMT induction of A549 cells enhanced CpG ODN uptake and CpG ODN-induced production of IL-6, IL-8 and MCP-1. These results suggest that EMT plays an important role in exacerbation in asthmatics with airway remodeling by enhancing sensitivity to extrinsic pathogens.