Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic.

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.

[A CASE OF BRONCHIAL ASTHMA CAUSED BY EXPOSURE TO ASPERGILLUS ORYZAE IN A JAPANESE RICE WINE BREWERY WORKER].

A-55-year-old man who have been working in a Sake (Japanese rice wine) brewer for 27 years, came to the outpatient clinic because cough, dyspnea, and wheeze gradually worsen. These symptoms occurred immediately after exposure to Aspergillus oryzae in the brewing process since age 43. A dust mask was required to reduce these symptoms, but that work was interrupted by exacerbation of these symptoms. These symptoms disappeared when he was away from the on-site work. The SMART therapy using combined inhaler of budesonide (ICS) with formoterol (LABA) was effective to reduce these symptoms. In serological test total IgE antibody and Aspergillus specific IgE antibodies increased, whereas Aspergillus precipitating antibody and Asp f 1 (a major allergen of Aspergillus fumigatus) specific IgE antibody were negative. Eosinophilia in peripheral blood was not observed, and FeNO was not increased. Values of peak expiratory flow was reduced by 20.8% after exposure to Aspergillus oryzae in that work. Lung function test including reversibility test was intact, but FEV1 was fluctuated up to 400mL (15.9%) in the clinical course. Based on these variable clinical manifestations, laboratory data, and lung function test findings, this case was diagnosed as adult-onset atopic (Aspergillus-sensitized) bronchial asthma without allergic bronchopulmonary aspergillosis. Involvement of eosinophilic inflammation is unknown. Allergen may be considered to be Aspergillus oryzae, because these symptoms do not occur in any environment without exposure to Aspergillus oryzae. This patient is the first case of occupational asthma related to Aspergillus oryzae in a Japanese rise wine brewer.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Usefulness of diurnal variation of fractional exhaled nitric oxide for predicting early therapeutic response to asthma treatment.

OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is considered to be an adjunct for asthma management, although its usefulness remains controversial. Therefore, it may be necessary for new approaches to use FeNO for asthma management. We evaluated whether diurnal variations of FeNO can predict response to asthma treatment. METHODS: This pilot study consisted of 22 uncontrolled asthmatics and 16 healthy subjects. FeNO and peak expiratory flow (PEF) were measured by themselves twice daily at home for three weeks (asthmatics) or two weeks (healthy subjects), and daily mean and diurnal variations of FeNO and PEF levels were calculated. In uncontrolled asthmatics, treatment was intensified a week after study entry, and then control status was reevaluated after three to four weeks. Asthmatics were then divided into two groups; good or poor responders. RESULTS: Diurnal variations of FeNO levels, as well as daily mean FeNO and PEF levels, in uncontrolled asthmatics before intensive treatment were significantly higher than those in healthy subjects, regardless of treatment response (p < 0.01). Furthermore, in the good responders, diurnal variations of FeNO levels were significantly decreased in the 1st week (p < 0.05) of intensive treatment, whereas the daily mean FeNO levels significantly dropped in the 2nd week (p < 0.05). In the poor responders, no such changes were observed in FeNO levels. In terms of PEF, only the daily mean levels were significantly elevated after the initiation of intensive treatment, regardless of treatment response. CONCLUSIONS: Diurnal variations of FeNO may contribute to predicting early therapeutic response to asthma treatment.

[A CASE OF ALLERGIC RHINITIS WHO HAS DEVELOPED EOSINOPHILIC PNEUMONIA, FOLLOWED BY EOSINOPHILIC CELLULITIS].

A-68-year-old man, who has allergic rhinitis with peripheral blood eosinophilia, hospitalized because of fever of unknown origin in May 2020. Five days after antibiotics were given, itchy exanthema occurred, followed by gland glass opacity on both lungs with bilateral pleural effusions. Since acute respiratory failure developed, bronchoscopy was hard to carry out. However, this case was considered acute eosinophilic pneumonia induced by antibiotics, based on radiological findings and laboratory data. Therefore, steroid pulse therapy using intravenous administration of methylprednisolone started, and this therapy was effective. Since these chest shadows and hypoxia were disappeared in two weeks, the amount of steroid was gradually reduced, however, eosinophilic pneumonia recurred once during this course. After discharge in June 2020, this patient came to the outpatient department. When oral administration of prednisolone was decreased less than 2.5mg/day, redness and swelling with slight itch were appeared in the left forearm in September 2020. Histological findings from shin biopsy showed that eosinophils excessively invade to the dermis without angiitis. Although flame figure was not observed in the specimen, we considered that this case has developed eosinophilic cellulitis, based on the clinical manifestation and pathological findings. When prednisolone was increased to 30mg/day, these symptoms were improved, and then prednisolone was gradually reduced. After that, recurrences of these diseases did not occur during the observation period. This case may be diagnosed as hypereosinophilic syndrome since eosinophilic pneumonia and eosinophilic cellulitis caused continuously by recruitment of eosinophils to lung and skin.

Association Between Sleep Characteristics and Asthma Control in Middle-Aged and Older Adults: A Prospective Cohort Study.

BACKGROUND: Nocturnal asthma symptoms are a well-known feature of sleep disturbance. However, there are few reports on the association between sleep-related characteristics and asthma exacerbation. The aim of the current prospective observational study was to explore the factors while sleeping associated with future asthma exacerbation. MATERIALS AND METHODS: At baseline, adult asthmatics underwent home sleep monitoring by a Watch-PAT instrument and then they were prospectively followed-up for the occurrence of exacerbations. The number of asthma exacerbation was observed over a period of one year, and multivariable analyses of the factors associated with asthma exacerbation were performed. RESULTS: A total of 62 asthmatic subjects were enrolled (mean age 62.1 years), 59 of whom were finally included in the prospective observational study. Obstructive sleep apnea (defined by an apnea-hypopnea index based on peripheral arterial tone more than 5 times/hour) were observed in 81% of the subjects. During the one-year monitoring period, 14 of the 59 subjects (24%) used occasional systemic corticosteroids for their exacerbation asthma (worsened group) while the other 45 subjects did not experience asthma exacerbation (stable group). A comparison of the baseline clinical characteristics and sleep-related data between the two groups, mean forced expiratory volume one second percent (FEV1/FVC), mean baseline Asthma Control Test (ACT) score, median pAHI value, and median oxygen desaturation index value were significantly lower in the worsened group than those in the stable group. Additionally, mean prevalence of the left lateral decubitus (LLD) position in sleep monitoring were significantly higher in the worsened group than that in the stable group. Among the independent variables, baseline asthma severity, ACT score, and the LLD position showed significant associations with asthma exacerbation. DISCUSSION/CONCLUSION: The present study identified that sleeping in the LLD position was also associated with asthma exacerbation.

Monomorphic Epitheliotropic Intestinal T-cell Lymphoma Involving the Lung and Brain: A Rare Case Study.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a primary intestinal T-cell lymphoma and other organ involvement is very rare. A rare case of MEITL involving the lung and brain is herein reported. The patient developed panperitonitis with a small intestinal perforation, and emergency surgery was performed. The pathological findings from the surgical specimens demonstrated atypical lymphoid cells which were positive for CD3, CD8, and CD56. Moreover, the pathological findings of lung specimens taken by bronchoscopy were consistent with those of the small intestine. It is therefore important to include the possibility of MEITL in the differential diagnosis of cancer patients.

Clinical significance of thyroid hormone and antibodies in patients with idiopathic interstitial pneumonia.

BACKGROUND: Hypothyroidism was recently reported to be common and to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In addition, a high prevalence of hypothyroidism was shown in patients with idiopathic pleuroparenchymal fibroelastosis. However, in idiopathic interstitial pneumonia (IIP), a clinical significance of thyroid function has not been clarified in detail. The goal of this study was to investigate the clinical significance of thyroid function and the presence of thyroid antibodies in IIP. METHODS: We have reviewed IIP patients, and analyzed the positivity of thyroid antibodies at first. Next, the relationship of clinical characteristics with thyroid function and the positivity of thyroid antibodies was analyzed. Lastly, the positivity of thyroid antibodies and other autoantibodies was evaluated. RESULTS: In IIP patients, thyroglobulin and thyroid peroxidase antibodies were positive in 17 and 16%, respectively, and 22% of patients had either or both antibodies. Subclinical and/or overt hypothyroidism was confirmed in 7% of IIP patients. The free thyrotropin level had a significant positive correlation with vital capacity and a significant negative correlation with the C-reactive protein and surfactant protein-A levels, and erythrocyte sedimentation ratio (ESR). In addition, autoantibodies suggestive of connective tissue diseases (CTDs) were positive in more than two thirds of IIP patients with the thyroid antibody, and the positive rate of antinuclear and proteinase-3 anti-neutrophil cytoplasmic antibodies was significantly higher in IIP patients with thyroid antibodies than those without the antibodies. CONCLUSIONS: Although thyroid dysfunction is not frequent, thyroid hormones and thyroid antibodies are possibly involved in the pathogenesis of IIP and their evaluation may be clinically useful to identify the clinical phenotype of IIP with autoimmune features.

Comparison of fractional exhaled nitric oxide levels measured by different analyzers produced by different manufacturers.

Objective: Fractional exhaled nitric oxide (FeNO) is widely used as a biomarker of allergic airway inflammation. At present, both stationary chemiluminescence and portable electrochemical analyzers produced by different manufacturers are available. However, it remains debatable whether those analyzers are comparable to each other. We compare FeNO levels obtained by different analyzers.Methods: For the first study, 153 subjects were enrolled to compare differences in FeNO levels measured using three analyzers (NA623NP®, NObreath®, and NIOX MINO®) which were produced by different manufacturers. For the second study, 30 subjects were recruited to compare FeNO levels obtained by the two analyzers (NIOX MINO® and NIOX VERO®) produced by the same manufacturer. FeNO was measured twice using each analyzer in random order.Results: FeNO levels obtained using the NIOX MINO® and NObreath® were more variable than those measured using the NA623NP®. There were strong positive correlations in FeNO levels measured by the NA623NP®, NIOX MINO®, and NObreath® (p < 0.001). The NA623NP® and NIOX MINO® provided the highest and lowest FeNO levels, respectively; whereas, those obtained by NObreath® were intermediate. No significant differences were observed in FeNO levels obtained using the NIOX MINO® and NIOX VERO®.Conclusions: FeNO levels measured by the NIOX MINO® and NIOX VERO®, both of which were produced by the same manufacturer, have comparability. However, significant differences in FeNO levels exist when measured by analyzers manufactured by different manufacturers. This should be taken into account for FeNO measurement.

Clinical Characteristics of Cough Frequency Patterns in Patients with and without Asthma.

BACKGROUND: Cough is a frequent symptom of asthma. Cough frequency (CoFr) monitoring devices are now available to objectively measure cough counts and offer a novel endpoint to assess asthma. However, little is known about CoFr in asthma. OBJECTIVE: The aims were, first, to determine whether unique features of CoFr exist in asthmatic and nonasthmatic patients and, secondly, to evaluate relationships between CoFr and pathophysiological parameters of asthma. METHODS: In the current study, 73 asthmatic and 63 nonasthmatic patients suffering from persistent cough were enrolled. At study entry, the Leicester Cough Questionnaire (LCQ health status), cough visual analog scale (VAS), Leicester Cough Monitor (LCM), fractional exhaled nitric oxide (FeNO) measurements, and spirometry were performed. In asthmatic patients, the bronchial hyperresponsiveness (BHR) test was conducted if applicable. In 28 asthmatic and 17 nonasthmatic patients, LCQ, VAS, and LCM were examined before and after treatment. RESULTS: CoFr during nighttime (asleep) was significantly higher in asthmatic patients than in nonasthmatic patients. Twenty-four-hour CoFr significantly decreased after appropriate treatment and was correlated with changes in VAS and LCQ in all patients. The improvement in cough in asthmatic patients was greater during nighttime than during daytime (awake). CoFr in asthmatic patients was significantly correlated with BHR, but not with FeNO. CONCLUSIONS: In asthmatic patients, nocturnal CoFr can be associated with BHR, was significantly higher before treatment, but improved more after treatment compared with nonasthmatic patients. Monitoring nocturnal CoFr may provide unique and valuable information on making an early prediction of therapeutic effects in asthma.

A case of primary lung squamous cell carcinoma mimicking malignant mesothelioma producing granulocyte colony stimulating factor with chemotherapy (cisplatin and gemcitabine)-associated thrombotic thrombocytopenic purpura (TTP); An autopsy case report.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy. In recent years, an extensive variety of drugs, including certain cytotoxic agents, have been reported to be associated with TTP. Additionally, several studies have reported that granulocyte colony-stimulating factor (G-CSF) was produced by lung carcinoma. G-CSF-producing carcinoma also produces various other cytokines, which may cause vascular endothelial damage and trigger TTP development. However, there has been no report describing G-CSF-producing carcinoma combined with TTP. We report a rare case of pseudomesothliomatous squamous cell lung carcinoma producing G-CSF along with chemotherapy associated TTP. MATERIALS AND METHODS: A 66-year-old man with pseudomesotheliomatous primary squamous cell lung carcinoma was treated with chemotherapy consisting of cisplatin and gemcitabine as the first line treatment. However, thrombocytopenia, acute renal dysfunction and acute respiratory failure occurred after starting the first chemotherapy cycle. As a result, the patient died, and an autopsy was performed. RESULTS: According to the autopsy findings, a diagnosis of primary lung squamous cell carcinoma producing G-CSF associated with TTP was made. CONCLUSION: Chemotherapy-related TTP should be considered when anemia and thrombocytopenia progress rapidly in patients who are under chemotherapy treatment. Furthermore, the current case may provide a possible link between TTP and G-CSF-producing tumor.

Serum decorin is a potential prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Decorin is a small leucine-rich repeat proteoglycan that plays a critical role in collagen fibrillogenesis, and regulates inflammation, wound healing and angiogenesis. In idiopathic pulmonary fibrosis (IPF), decorin is expressed in fibrotic lesions; furthermore, intratracheal gene transfer of decorin has been demonstrated to inhibit bleomycin-induced pulmonary fibrosis. Although these results suggest the critical role of decorin in pulmonary fibrosis, the role of decorin in the acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) has not been clarified in detail. Thus, the goal of this study was to determine the role of decorin in AE-IIP. METHODS: We retrospectively analyzed AE-IIP patients who had been admitted to our hospital. First, serum decorin levels were compared among patients with AE-IIP, patients with stable idiopathic interstitial pneumonia (SD-IIP), and healthy subjects. Next, the relationship between serum decorin levels and clinical parameters was analyzed in AE-IIP patients. Finally, the association between serum decorin levels and prognosis was evaluated in AE-IIP patients. IIP was divided into IPF and non-IPF, according to the published guidelines. RESULTS: The serum decorin levels of AE-IIP patients were significantly lower than those of both healthy subjects and SD-IIP patients. Serum decorin levels were not related with the clinical parameters and prognosis, when all IIP patients were analyzed. In IPF patients, serum decorin levels had a significant correlation with oxygenation, and IPF patients with low serum decorin levels had a significantly higher survival rate than those with high serum decorin levels. CONCLUSIONS: Serum decorin levels are a potential prognostic biomarker in AE-IPF.

A Case of Eosinophilic Granulomatosis with Polyangiitis Complicated with A IgG4 Related Disease Like Symptoms.

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA) complicated with a IgG4 related disease like symptoms presenting as eyelid swellings. In the present case, the serum level of IgG4 and the ratio of IgG4 to IgG were generally increased by the disease course of EGPA. Considering the course of clinical symptoms, there is a possibility that orbital manifestations were one of the clinical features during the disease course of EGPA while the histological features of right eyelid tissue and other ocular manifestations were consistent with the diagnosis of IgG4 related disease.

The clinical role of fractional exhaled nitric oxide in asthma control.

BACKGROUND: The potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma. OBJECTIVE: To explore the clinical role of FeNO in asthmatic treatment. METHODS: We evaluated whether the mean or change of FeNO levels in the treatment period is associated with other conventional control parameters and predicted some clinical outcomes of asthma. We retrospectively analyzed the mean and percentage change of FeNO levels in the first 5 measurements at our hospital. RESULTS: The study found a significantly strong correlation between FeNO level at diagnosis and the largest changes of FeNO values from diagnosis. No significant correlations were observed between FeNO levels and other parameters (Asthma Control Test [ACT] score or forced expiratory volume in one second [FEV1]) in mean and percentage change of values under treatment of asthma; however, significant positive correlations were found between ACT scores and FEV1. The mean FeNO level revealed a significant negative correlation with an annual change in FEV1 in individuals with asthma who were followed up for more than 2 years. Both the mean ACT score and percent predicted FEV1 revealed a significant negative correlation with occasional use of systemic corticosteroids. CONCLUSION: During conventional treatment of asthma, the largest changes of FeNO values from diagnosis were strongly correlated with FeNO levels at diagnosis. As for the unlikely conventional parameters, no significant associations were observed between FeNO levels and deterioration of asthma during the treatment periods. An elevated mean FeNO level may be a marker of decreased lung function in individuals with asthma.

The association between risk of airflow limitation and serum uric acid measured at medical health check-ups.

The prevalence of COPD and asthma is increasing all over the world; however, their morbidities are thought to be greatly underestimated because of unawareness of patients' conditions and respiratory symptoms. Spirometry is useful for the early detection of COPD and asthma with airflow limitation (AL), although it is not yet widely used for screening in epidemiological and primary care settings. A simple predictive marker used in combination with spirometry for AL is expected to be established. In medical health check-ups, serum uric acid (s-UA) is measured when screening for gout and has recently been suggested to have an association with several respiratory disorders, including asthma and COPD. However, whether s-UA influences the development of AL remains unclear. Therefore, the aims of this study were to examine the relationship between AL and s-UA and to investigate s-UA as a potential auxiliary marker for predicting AL risk in medical health check-ups. A total of 8,662 subjects aged >40 years were included. They were administered a simple questionnaire and assessed using pulmonary function tests, blood pressure (BP) measurements, and blood samplings. One hundred and fifty-six subjects (1.8%) had AL, just 29% of whom had experienced respiratory symptoms. The subjects with AL had significantly higher s-UA levels compared with never-smoking subjects without AL. Forced expiratory volume in 1 second (FEV1) %predicted showed significant correlations with age, smoking index, body mass index (BMI), mean BP, white blood cells, hemoglobin A1c, s-UA, and high-density lipoprotein cholesterol. In multiple logistic regression analysis, s-UA, in addition to age, smoking index, respiratory symptoms, and BMI, was independently associated with AL. In conclusion, elevated s-UA levels, together with respiratory symptoms, high smoking index, and weight loss, may epidemiologically predict the development of AL risk.

Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics.

BACKGROUND: Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment. METHODS: Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared. RESULTS: In 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels. CONCLUSIONS: The number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.