Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema.

Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change.

Comprehensive Gene Expression Signature Using RNA-Seq in Airways of Mouse Model of Severe Asthma with Fungal Sensitization.

INTRODUCTION: Inhalation of fungal allergens induces airway epithelial damage following airway inflammation and excessive mucus secretion, which can lead to severe asthma with fungal sensitization (SAFS). Comprehensive gene expression analysis in Alternaria-exposed mouse airways, a model of SAFS, has not been conducted. METHODS: BALB/c mice received intranasal administration of Alternaria extract or phosphate-buffered saline twice a week for 6 weeks. Lung sections and bronchoalveolar lavage fluid were obtained to assess airway inflammation. RNA-Seq in the central airway was performed, and gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted for pathway analyses. An in vitro experiment using human airway epithelial cell 16HBE14o- was performed to validate the RNA-Seq findings. RESULTS: Eosinophilic airway inflammation with mucus overproduction and airway remodeling was observed in mice exposed to Alternaria. RNA-Seq analysis revealed 403 upregulated and 108 downregulated genes in airways of Alternaria-exposed mice. In GO analysis, the functions of immunoglobulin (Ig) receptor binding, Ig production, inflammatory response, and T-cell activation were upregulated, while those of keratinization and defense response to other organisms were downregulated. GSEA revealed positive enrichment in T-cell receptor complex, immunological synapse, antigen binding, mast cell activation, and Ig receptor binding, and negative enrichment in keratinization and cornification in Alternaria-exposed mice relative to control. Alternaria exposure to 16HBE14o- cells validated the downregulation of epithelial keratinization-related genes, including SPRR1A, SPRR1B, and KRT6B. CONCLUSION: RNA-Seq analysis showed that Alternaria exposure induced inflammatory response and impaired defense mechanisms in mice airway epithelium, which might be therapeutic targets for SAFS.

Downregulation of type III interferons in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.

Comparison between conventional and compressed sensing cine cardiovascular magnetic resonance for feature tracking global circumferential strain assessment.

BACKGROUND: Feature tracking (FT) has become an established tool for cardiovascular magnetic resonance (CMR)-based strain analysis. Recently, the compressed sensing (CS) technique has been applied to cine CMR, which has drastically reduced its acquisition time. However, the effects of CS imaging on FT strain analysis need to be carefully studied. This study aimed to investigate the use of CS cine CMR for FT strain analysis compared to conventional cine CMR. METHODS: Sixty-five patients with different left ventricular (LV) pathologies underwent both retrospective conventional cine CMR and prospective CS cine CMR using a prototype sequence with the comparable temporal and spatial resolution at 3 T. Eight short-axis cine images covering the entire LV were obtained and used for LV volume assessment and FT strain analysis. Prospective CS cine CMR data over 1.5 heartbeats were acquired to capture the complete end-diastolic data between the first and second heartbeats. LV volume assessment and FT strain analysis were performed using a dedicated software (ci42; Circle Cardiovasacular Imaging, Calgary, Canada), and the global circumferential strain (GCS) and GCS rate were calculated from both cine CMR sequences. RESULTS: There were no significant differences in the GCS (- 17.1% [- 11.7, - 19.5] vs. - 16.1% [- 11.9, - 19.3; p = 0.508) and GCS rate (- 0.8 [- 0.6, - 1.0] vs. - 0.8 [- 0.7, - 1.0]; p = 0.587) obtained using conventional and CS cine CMR. The GCS obtained using both methods showed excellent agreement (y = 0.99x - 0.24; r = 0.95; p < 0.001). The Bland-Altman analysis revealed that the mean difference in the GCS between the conventional and CS cine CMR was 0.1% with limits of agreement between -2.8% and 3.0%. No significant differences were found in all LV volume assessment between both types of cine CMR. CONCLUSION: CS cine CMR could be used for GCS assessment by CMR-FT as well as conventional cine CMR. This finding further enhances the clinical utility of high-speed CS cine CMR imaging.

Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease.

The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p < 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p < 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.

The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

What is the mid-wall linear high intensity "lesion" on cardiovascular magnetic resonance late gadolinium enhancement?

BACKGROUND: Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) is a valuable technique for detecting myocardial disorders and fibrosis. However, we sometimes observe a linear, mid-wall high intensity signal in the basal septum in the short axis view, which often presents diagnostic difficulties in the clinical setting. The purpose of this study was to compare the linear, mid-wall high intensity in the basal septum identified by LGE with the anterior septal perforator arteries identified by coronary computed tomography angiography (CorCTA). METHODS: We retrospectively selected 148 patients who underwent both CorCTA and CMR LGE within 1 year. In the interpretation of LGE, we defined a positive linear high intensity (LHI+) as follows: ① LHI in the basal septum and ② observable for 1.5 cm or more. All other patients were defined as a negative LHI (LHI-). In LHI+ patients, we assessed the correlation between the LHI length and the septal perforator artery length on CorCTA. We also compared the length of the septal perforator artery on CorCTA between LHI+ patients and LHI- patients. RESULTS: A population of 111 patients were used for further analysis. Among these , there were 55 LHI+ patients and 56 LHI- patients. In LHI+ patients, linear regression analysis revealed that there was a good agreement between LGE LHI and septal perforator arteries by CorCTA in terms of length measurements. The measured length of the anterior septal perforator arteries was significantly shorter in LHI- patients than in LHI+ patients (10 ± 8 mm vs. 21 ± 8 mm; P < 0.05). CONCLUSIONS: The LHI observed in the basal septum on short axis LGE may reflect contrast enhancement of the anterior septal perforator arteries. It is important to interpret this septal LHI against knowledge of anatomic structure, to avoid misinterpretations of LGE and prevent misdiagnosis.

Feasibility of contrast-enhanced coronary artery magnetic resonance angiography using compressed sensing.

BACKGROUND: Coronary magnetic resonance angiography (CMRA) is a promising technique for assessing the coronary arteries. However, a disadvantage of CMRA is the comparatively long acquisition time. Compressed sensing (CS) can considerably reduce the scan time. The aim of this study was to verify the feasibility of CS CMRA scanning during the waiting time between contrast injection and late gadolinium enhancement (LGE) scan in a clinical protocol. METHODS: Fifty clinical patients underwent contrast-enhanced CS CMRA and conventional CMRA on a 3 T CMR scanner. After contrast injection, CS CMRA was scanned during the waiting time for LGE CMR. A conventional CMRA scan was performed after LGE CMR. We assessed acquisition times and coronary artery image quality for each segment on a 4-point scale. Visible vessel length, sharpness and diameter of right (RCA), left anterior descending (LAD), and left circumflex (LCX) coronary arteries were also quantitatively compared among the scans. RESULTS: All CS CMRA scans were successfully performed within the LGE waiting time. The median total scan time was 207 s (163, 259 s) for CS and 785 s (698, 975 s) for conventional CMRA (p < 0.001). No significant differences were observed in image quality scores, vessel length measurements, sharpness, and diameter between CS and conventional CMRA. CONCLUSIONS: We could achieve all CS CMRA scans within the LGE waiting time. Contrast-enhanced CS CMRA could considerably shorten the scan time while maintaining image quality compared with conventional CMRA.

Oral meal intake as a prognostic predictor of community-acquired pneumonia: A retrospective cohort study.

INTRODUCTION: The association between oral intake volume and prognosis has not been studied in hospitalized patients with community-acquired pneumonia (CAP). METHODS: We retrospectively examined 503 hospitalized CAP patients to evaluate whether early-phase meal intake (EMI) (within the first 24 h after hospitalization) and maximum meal intake (MMI) (on the day during hospitalization) are useful prognostic predictors. RESULTS: Of the 503 patients, 40 (8.0%) died within 30 days. Area under the curve (AUC) for prognosis was comparable between EMI, A-DROP, and serum albumin [EMI: 0.80, 95% confidence interval (CI) 0.75-0.84; A-DROP: 0.77, 95% CI 0.71-0.83; Serum albumin: 0.72, 95% CI 0.64-0.79]. Mortality rate was <1% in patients with EMI ≥ 50%. Univariate analysis showed that patients with EMI < 50% showed poor prognosis [odds ratio 53.4, 95% CI 7.2-392.2]. Multivariate analysis showed that EMI was an independent prognostic predictor [odds ratio 23.6, 95% CI 3.11-179.7]. AUC of MMI for prognosis was 0.94 (95% CI 0.91-0.96); mortality rate was <1% for patients who ingested ≥50% of meals on any day during hospitalization. We defined ingesting ≥50% of meals on any day during hospitalization as oral intake stability. Multivariate analyses revealed an association between oral intake stability and prognosis. Odds ratio of oral intake stability for prognosis was higher than that of conventional evaluations (vital sign and CRP level stability). Fewer days were required to reach oral intake stability than to reach vital sign and CRP level stability. CONCLUSIONS: Oral intake is a simple, non-invasive, cost-free, and powerful prognostic predictor for patients with CAP.

Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma.

PURPOSE: Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma. METHODS: Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed. RESULTS: OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA. CONCLUSIONS: These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.

Safety and Efficacy of Nontuberculous Mycobacteria Treatment among Elderly Patients.

Background and objectives: Incidence rates of pulmonary nontuberculous mycobacterial (NTM) disease have been increasing, especially in the elderly population. Given the limited evidence regarding the safety and efficacy of NTM treatment, this study aimed to evaluate the same among elderly patients. Material and methods: Patients diagnosed with NTM disease at a tertiary hospital from January 2007 to December 2017 were enrolled and data were then retrospectively collected. Data of elderly patients who received antimycobacterial treatment were then analyzed. Results: A total of 161 patients satisfied the diagnostic criteria for NTM disease. There were 40 elderly patients who received treatments. Of the patients, 60% received the guideline oriented standard regimens. Single drug regimens were administered to 22.5% of patients. Only 55.0% of the patients were able to continue any treatment. Treatment-related discontinuation was observed in 44.4% of discontinued or changed patients. There were no significant differences in the characteristics of patients with or without adverse events. Patients who were able to continue the treatment for >12 months had a lower proportion of activities of daily living (ADL) disability (nine in 18, 50.0% vs. three in 22, 13.6%, p = 0.018) and heart disease (six in 18, 33.3% vs. 1/22, 4.6%, p = 0.033). Sputum culture conversion was achieved in 28 out of 40 (70.0%) elderly patients treated, and those who achieved sputum culture conversion had more standard regimens prescribed than those who failed sputum culture conversion (21 in 28, 75% vs. 3 in 12, 25%; p = 0.005). Conclusion: Age may not be an obstacle for receiving the benefits of the treatment of NTM disease with a precise evaluation of patient's comorbidities. Furthermore, elderly patients without heart disease and ADL disability may have better rate of continuing the NTM treatment. The current study suggested that selecting standard regimens to treat pulmonary NTM is important for elderly patients.

Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide.

BACKGROUND: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD's usefulness if taken after a virus has already infected airway tissue. OBJECTIVE: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD's experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. CONCLUSION: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. CONCLUSION: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

On-Site Computed Tomography-Derived Fractional Flow Reserve Using a Machine-Learning Algorithm　- Clinical Effectiveness in a Retrospective Multicenter Cohort.

BACKGROUND: This study evaluated the diagnostic capability of on-site coronary computed tomography-derived computational fractional flow reserve (CT-FFR) determinations for detecting coronary artery disease (CAD), as assessed by invasive fractional flow reserve (FFR).Methods and Results:Seventy-four patients with coronary artery calcium scores <1,500 who underwent coronary CT angiography (CTA) and invasive FFR measurements within 90 days were retrospectively reviewed. CT-FFR was computed using a prototype machine-learning (ML) algorithm in 91 vessels; 47 vessels of 42 patients were determined to have significant CAD (FFR ≤0.8). Correlation between CT-FFR and FFR was good (r=0.786, P<0.001). Per-vessel area under the curve was significantly larger for CT-FFR (0.907, 95% confidence interval: 0.828-0.958) than for CTA stenosis ≥50% (0.595, 0.487-0.697) or ≥70% (0.603, 0.495-0.705) (both P<0.001). Standard coronary CTA classifications recommended further functional tests in 57 patients with moderate or worse stenosis on CTA. CT-FFR analysis (mean analysis time: 16.4±7.5 min) corrected the standard coronary CTA classification in 18 of 74 patients and confirmed it in 45 of 74 patients. Thus, the per-patient diagnostic accuracy of the classifications was improved from 66% (54-77%) to 85% (75-92%). CONCLUSIONS: On-site CT-FFR based on a ML algorithm can provide good diagnostic performance for detecting hemodynamically significant CAD, suggesting the high value of coronary CTA for selected patients in clinical practice.

Acute exacerbation of idiopathic pulmonary fibrosis induced by pertussis: the first case report.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe condition with limited treatment strategies. Although respiratory infection is a major cause of AE-IPF, no reports have indicated pertussis infection as a cause. Here we report two cases of pertussis infection-induced AE-IPF. CASE PRESENTATION: Both patients presented with a chief complaint of acute respiratory distress and were previously diagnosed with idiopathic pulmonary fibrosis (IPF). Neither patient had received any pertussis vaccination since adolescence. Both patients were diagnosed with AE-IPF accompanying acute pertussis infection based on chest computed tomography and serum pertussis toxin antibody > 100 EU/mL. Both patients were treated with macrolide antibiotics and systemic corticosteroids. Both patients were able to be discharged and return home. CONCLUSIONS: The presence of pertussis infection in AE-IPF can present a diagnostic challenge, as coughing accompanying pertussis may be difficult to distinguish from IPF-associated coughing. Pertussis infection should be assayed in AE-IPF patients. Since pertussis can be prevented with vaccination and is expected to be affected by antibiotics, consideration of pertussis infection as a causative virulent factor of AE-IPF may be important for management of subjects with IPF.

Predicting future risk of exacerbations in Japanese patients with adult asthma: A prospective 1-year follow up study.

BACKGROUND: To avoid future risk is a definitive goal of long-term asthma management. Exacerbations are considered to be the most relevant future risk in real life asthma management. Few comparative studies have evaluated the risk factors associated with exacerbations in Japanese patients with asthma. METHODS: We performed the prospective 1-year follow up study in Japanese patients with adult asthma. A total of 189 patients with asthma were enrolled and followed up for 1 year. Finally, 181 patients completed the study protocol. RESULTS: Of 181 patients, 43 patients (23.8%) had exacerbations during the follow-up period. Among the 45 patients who had exacerbations during the preceding year, 32 patients (71.1%) had exacerbations. Prevalence of patients with previous exacerbations and those with previous admissions were significantly higher in patients with exacerbations than those with no exacerbation. Logistic regression analysis also identified a significant association between exacerbations during the follow-up period and exacerbations during the preceding year, admissions during the preceding 3 years, ACT score below 20, low %FVC (<80%), or low FEV1 (<70%), respectively. Of the 55 patients with severe asthma, 29 patients (52.7%) had exacerbations. Among the 36 patients with severe asthma with previous exacerbations, 26 patients (72.2%) had exacerbations. The history of exacerbations during the preceding year was associated with a significantly increased risk of exacerbations both among the patients with severe asthma and those with non-severe asthma. CONCLUSIONS: This study implicated that exacerbations during the preceding year reliably predict future risk of exacerbations in Japanese patients with asthma.

Association between specific IgE to Staphylococcus aureus enterotoxins A and B and asthma control.

BACKGROUND: Recent studies have found that serum levels of Staphylococcus aureus enterotoxin (SE)-IgE are higher in patients with severe asthma compared with patients with nonsevere asthma. However, the association between SE-IgE and asthma control is not fully understood. Furthermore, SEA and SEB were the first reported SEs and subdivided into different groups. The influences of SEA-IgE and SEB-IgE on asthma control have not been elucidated. OBJECTIVE: To determine the relevance of SEA- and SEB-IgE in patients with adult asthma and to investigate the association of SEA-IgE, SEB-IgE, and asthma control, respectively. METHODS: The serum concentrations of SEA- and SEB-IgE in 172 adults with asthma were measured with a fluorescent enzyme immunoassay. RESULTS: The prevalence of SEA- and SEB-IgE was 16.2% and 22.1%, respectively. Total IgE levels and the prevalence of atopic dermatitis were higher in SEA-IgE- and SEB-IgE-positive patients than in SEA-IgE- and SEB-IgE-negative patients, respectively; more SEA-IgE- and SEB-IgE-positive patients owned pets. Sensitization to SEA was associated with a younger mean age and a younger mean age at asthma onset. Multiple regression analysis indicated an association between total IgE levels and SEB-IgE. The prevalence of poorly uncontrolled asthma was significantly higher in SEA-IgE-positive patients than in SEA-IgE-negative patients. In addition, fractional exhaled nitric oxide levels were higher in SEA-IgE-positive patients than in SEA-IgE-negative patients. Logistic regression analysis also identified an association between SEA-IgE and poor asthma control. CONCLUSION: Our findings indicate that sensitization to SE, in particular SEA rather than SEB, is associated with poor asthma control in adults with asthma.