Super-responder and clinical remission in patients with asthma on treatment with single biologic therapy or cycling therapy using dupilumab in a real-world setting.

BACKGROUND: Regarding the therapeutic target in asthma, super-responder status (SR) is a status without systemic corticosteroids. Recently, clinical remission (CR), being a status of prolonged absence of asthma symptoms without systemic corticosteroids and/or normal pulmonary function, has gained attention as a new therapeutic target in asthma. Here, we examined the percentage and features of asthma patients on treatment with dupilumab showing SR and CR. MATERIALS AND METHODS: 49 asthma patients used subcutaneous dupilumab for > 1 year between April 2019 and November 2022. The status of SR and CR for 1 year was evaluated. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids were classified as SR. CR was defined using three definitions based on changes in asthma symptoms and pulmonary function in addition to achieving SR for 1 year: CR without pulmonary function criteria (CR w/o F), fulfilment of asthma symptom improvement (asthma control questionnaire score < 0.75 or asthma control test score ≥ 23); and CR-70 or CR-80, pulmonary function improvement (%forced expiratory volume in 1 second ≥ 70% or ≥ 80%) in addition to achieving CR w/o F, respectively. RESULTS: 38 (77.6%), 22 (44.9%), 13 (26.5%), 12 (24.5%) of patients had SR, CR w/o F, CR-70, and CR-80, respectively. Severe eosinophilic chronic rhinosinusitis was significantly more found in patients with SR and CR based on all three definitions than in those without. CONCLUSION: This study identified the percentage and features of patients on treatment with dupilumab showing SR and CR in a real-world setting. The outcome beyond CR on biologic treatment should be clarified.

Role of eosinophilic chronic rhinosinusitis in switching to benralizumab treatment in mepolizumab responders.

BACKGROUND: There are currently three anti-interleukin-5 (IL-5) pathway-directed therapies: mepolizumab, reslizumab, and benralizumab. Of these, benralizumab was most recently approved. Benralizumab is administered every 8 weeks after an initial 3 doses given every 4 weeks, whereas mepolizumab and reslizumab are administered every 4 weeks. This convenience in benralizumab administration indicates that it is potentially beneficial for patients. Therefore, we potentially have an opportunity to change to benralizumab in patients who responded to mepolizumab or reslizumab. However, other than eosinophil levels, factors that could predict patients responding to anti-IL-5 pathway-directed therapies have been unknown. In this study, we examine the clinical characteristics of mepolizumab responders who achieved successful switching to benralizumab. MATERIALS AND METHODS: A total of 18 consecutive severe asthmatic patients treated with sequential mepolizumab and benralizumab, each for at least 1 year, were enrolled in this study. This study was a single-center case series. Patients were defined as having achieved successful switching to benralizumab if they satisfied either of the following for 1 year before and after the benralizumab treatment: (1) they experienced no exacerbation; or (2) they experienced no exacerbation and discontinued oral corticosteroids. RESULTS: All 18 patients responded to mepolizumab treatment, and 11 of them achieved successful switching to benralizumab. The proportion of patients who achieved successful switching to benralizumab was higher in patients with eosinophilic chronic rhinosinusitis (ECRS) than in those without (76.9 vs. 20.0%; p = 0.025). CONCLUSION: Our findings imply that in responders to mepolizumab, there may be a higher response rate to benralizumab in patients with ECRS than in those without.

Critical role of CCL4 in eosinophil recruitment into the airway.

BACKGROUND: Excessive eosinophil airway infiltration is a clinically critical condition in some cases. Eosinophilic pneumonia (EP) is a pulmonary condition involving eosinophil infiltration of the lungs. Although several chemokines, including eotaxin-1 (CCL11), RANTES (CCL5) and macrophage inflammatory protein 1ß (MIP-1ß or CCL4), have been detected in bronchoalveolar lavage fluid (BALF) from patients with EP, the pathophysiological mechanisms underlying EP, including potential relationships between eosinophils and CCL4, have not been fully elucidated. OBJECTIVE: To examine the involvement of CCL4 in eosinophilic airway inflammation. METHODS: We analysed supernatants of activated eosinophils and BALF from 16 patients with eosinophilic pneumonia (EP). Further, we examined the effects of CCL4 on eosinophil functions in vitro and those of anti-CCL4 neutralizing antibody in an in vivo model. RESULTS: We found that purified human eosinophils stimulated with IL-5 predominantly secreted CCL4 and that patients with EP had elevated CCL11 and CCL4 levels in BALF compared with samples from individuals without EP. Because CCL4 levels were more strongly correlated with eosinophil count and expression of eosinophil granule proteins than CCL11, in vitro experiments using purified eosinophils concentrated on the former chemokine. Interestingly, CCL4 acted as a chemoattractant for eosinophils. In a mouse model, administration of a CCL4-neutralizing antibody attenuated eosinophilic airway infiltration and airway hyperresponsiveness. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, these findings highlight an important role of CCL4 in the mechanisms underlying eosinophil recruitment into the airway and may provide a novel insight into this potential therapeutic target.

Effect of nasally exhaling budesonide/formoterol dry powder inhaled at "fast" inspiratory flow on eosinophilic chronic rhinosinusitis
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BACKGROUND: Budesonide (BUD)/formoterol (FM) dry powder inhaler has a feature that the fine particle fraction output is dependent on users' inspiratory flow rate. The aim of this study was to assess the amount of nasally exhaled BUD/FM inhaled in the different inspiratory flow rate. We also examined the effect of nasal exhalation of BUD/FM dry powder inhaled on radiographic evidence of sinonasal inflammation in asthmatic patients with eosinophilic chronic rhinosinusitis (ECRS). MATERIALS AND METHODS: The quantitative amount of nasally exhaled BUD/FM was analyzed by high-performance liquid chromatography in 3 healthy subjects. We retrospectively evaluated the effect of nasal exhalation of BUD/FM dry powder inhaled at > 60 L/min on radiographic evidence of sinonasal inflammation, which was assessed according to the Lund-Mackay staging (LMS) system, in 7 consecutive patients with asthma and ECRS. RESULTS: The amount of nasally exhaled BUD in the setting of inhaling BUD/FM dry powder inhaler at 60 L/min (subject 1: 25.8 ng/mL; subject 2: 37.3 ng/mL; subject 3: 30.0 ng/mL) was high compared to at 30 L/min (subject 1: 9.3 ng/mL; subject 2: 4.1 ng/mL; subject 3: 9.2 ng/mL) in each healthy subject. Nasal exhalation of BUD/FM dry powder significantly reduced total (p = 0.018) and ethmoid LMS scores (p = 0.0077). CONCLUSION: Nasal exhalation technique of BUD/FM dry powder inhaled at "fast" inspiratory flow has a potential of simultaneously treating asthma and ECRS.
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Replacement of SFC-DPI with SFC-MDI exhaled through the nose improves eosinophilic chronic rhinosinusitis in patients with bronchial asthma.

OBJECTIVE: Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is a refractory disease closely associated with bronchial asthma. We recently reported on the efficacy of ultra-fine particle inhaled corticosteroids (ICS) (hydrofluoroalkane-134a-beclomethasone dipropionate: HFA-BDP) exhalation through the nose (ETN) treatment for mild-to-moderate asthmatics with ECRS. However, the effect of HFA-BDP ETN was found to be transient in some cases with severe ECRS and asthma, requiring treatment with higher-dose ICS and long-acting ß2-agonists (LABA). Here, we present a case of refractory ECRS with severe asthma treated with a combination of high-dose ICS and LABA ETN, and we discuss the mechanisms for its effectiveness. METHODS: A 57-year-old man was treated with the combined regimen of HFA-BDP ETN and salmeterol/fluticasone combination (SFC) dry powder inhaler (DPI) for his refractory ECRS with severe asthma. For better control, we replaced SFC-DPI with SFC metered-dose inhaler (MDI) ETN and evaluated the clinical effect and corticosteroid sensitivity. We also examined the flow and deposition of fine particles released by SFC-MDI ETN. RESULTS: After switching to SFC-MDI ETN, the patient's conditions markedly resolved with the restoration of corticosteroid sensitivity and PP2A activity. The fine particles released by SFC-MDI ETN at least partially flowed out through the external nares and seemed to be deposited on the ethmoid sinus. CONCLUSION: Fine particle ICS/LABA ETN might be an additional therapeutic option for refractory ECRS with severe asthma and corticosteroid insensitivity.
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Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea.

PURPOSE: In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements. METHODS: Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy. RESULTS: Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable. CONCLUSIONS: In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.

Problems of elderly patients on inhalation therapy: Difference in problem recognition between patients and medical professionals.

BACKGROUND: There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals. METHODS: A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed. RESULTS: According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy. CONCLUSIONS: Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.

Residual exhaled nitric oxide elevation in asthmatics is associated with eosinophilic chronic rhinosinusitis.

OBJECTIVE: Eosinophilic chronic rhinosinusitis (ECRS) is as a subgroup of chronic rhinosinusitis (CRS) with nasal polyps. ECRS is a refractory disease closely related to bronchial asthma. Fractionated exhaled nitric oxide (FeNO) levels were reportedly elevated in some asthmatics with CRS after adequate treatment, suggesting that residual eosinophilic airway inflammation or ECRS might affect FeNO levels. METHODS: To investigate the association between asthma with ECRS and FeNO levels, we examined FeNO levels in 133 asthmatics (99 with ECRS and 34 without ECRS) and 13 patients with ECRS without asthma. The severity of asthma was defined by the Global Initiative for Asthma guidelines and that of sinusitis was evaluated by the sinus CT score based on the Lund-Mackay scale. RESULTS AND CONCLUSIONS: FeNO levels were elevated even in well-controlled asthmatics with ECRS, whereas asthmatics without ECRS and ECRS patients without asthma did not have high FeNO levels (>50 ppb). Although FeNO levels were not correlated with asthma severity, they were positively correlated with the sinus CT score. In asthmatics with ECRS, patients with higher FeNO levels had more severe ECRS and asthma. There is a possibility of having comorbid ECRS, particularly in asthmatics with high FeNO levels even after adequate treatment, including ICS, suggesting that asthma and ECRS may be closely associated as one airway disease with eosinophilic inflammation. Continual awareness of the coexistent ECRS is ideally recommended for asthmatics with high FeNO levels.

A novel therapeutic use of HFA-BDP metereddose inhaler for asthmatic patients with rhinosinusitis: Case series.

OBJECTIVE: Most asthmatics have been found to have rhinosinusitis (RS). Patients with ethmoid sinusitis, in particular, often suffer from an impaired sense of smell; this is clinically important and necessitates concurrent treatment for both asthma and RS. As a rational therapeutic strategy, we focused on a fine particle HFA-134abeclomethasone dipropionate (HFA-BDP) metered-dose inhaler. Because of its small size, the medication is still present in the exhaled breath after inhalation. METHODS: Five mild-to-moderate asthmatics with ethomoidpredominant sinusitis characterized by an impaired sense of smell and mild peripheral blood eosinophilia received a single-agent treatment with orally-inhaled HFA-BDP which was then exhaled through the nose. In addition, the stained small particles were created by an ultrasonic nebulizer and flow image of them during oral inhalation and nasal exhalation was evaluated by using nasal endoscopy. RESULTS: After treatment, the sense of smell was restored in all cases with a concomitant improvement in sinusitis as confirmed by computerized tomography. In addition, amelioration of peripheral blood eosinophilia as well as small airway obstruction as indicated by pulmonary function tests was observed. Macroscopical imaging revealed that small particles flow toward olfactory cleft during both the inhalation and exhalation phases. CONCLUSION: We have presented 5 cases of asthmatic patients with RS treated with a concurrent single therapy, HFA-BDP exhaled through the nose (ETN). A clinical trial must be considered to establish this new therapeutic strategy based on the concept of "one airway, one disease."

Favorable clinical course after discontinuation of omalizumab treatment in patients with allergic severe asthma: A real-world clinical practice.

The success rate of omalizumab discontinuation is 50-75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3-12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

[Impact of inhaled corticosteroid prescription at discharge from the emergency room on exacerbations of asthma in Japanese hospital].

BACKGROUND: Inhaled corticosteroid (ICS) therapy has been reported to improve relapses of asthma following emergency room (ER) discharge, but the benefits of ICS prescription at discharge from the ER are unclear. OBJECTIVE: To assess background of the patients who visit ER, and determine whether the prescription of ICS at ER reduces relapses in the patients with asthma. METHODS: A prospective multi-center cohort study was conducted at 32 Japanese ERs. Patients aged two to 82 years who visited ER with moderate to severe exacerbation of asthma underwent questionnaire and follow-up three and six months later. The primary observations were of the asthma-related hospitalizations, ER visits, and unscheduled visits. RESULTS: Among 343 asthma patients (Children: 120, Adults: 223), 33% of children and 12% of adult patients were classified as intermittent asthma, retrospectively. The patients with intermittent had the same rates of hospitalization (29.6%) and ER visits (46.2%) as those with persistent (hospitalization rate: 24.7%, ER visits: 53.1%, ns) before enrolled. The odds ratio for hospitalization in the patients received ICS at the discharge from the ER, compared with the patients who did not received ICS, yielded 0.256 (95% confidence interval, 0.069 to 0.942; p=0.040) by multinomial logistic regression model. CONCLUSION: Prescribing ICS at discharge from the ER to asthma patients is associated with the reduction of risk for asthma-related hospitalization. For patients discharged from the ER, including mild intermittent asthma, ICS might be prescribed.

HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps in Japanese. ECRS highly associated with asthma is a refractory eosinophilic airway inflammation and requires comprehensive care as part of the united airway concept. We recently reported a series of ECRS patients with asthma treated with fine-particle inhaled corticosteroid (ICS) exhalation through the nose (ETN). Objective: To evaluate fine-particle ICS ETN treatment as a potential therapeutic option in ECRS with asthma. Methods: Twenty-three patients with severe ECRS under refractory to intranasal corticosteroid treatment were randomized in a double-blind fashion to receive either HFA-134a-beclomethasone dipropionate (HFA-BDP) metered-dose inhaler (MDI) ETN (n = 11) or placebo MDI ETN (n = 12) for 4 weeks. Changes in nasal polyp score, computed tomographic (CT) score, smell test, and quality of life (QOL) score from baseline were assessed. Fractionated exhaled nitric oxide (FENO) was measured as a marker of eosinophilic airway inflammation. Response to corticosteroids was evaluated before and after treatment. Additionally, deposition of fine-particles was visualized using a particle deposition model. To examine the role of eosinophils on airway inflammation, BEAS-2B human bronchial epithelial cells were co-incubated with purified eosinophils to determine corticosteroid sensitivity. Results: HFA-BDP MDI ETN treatment improved all assessed clinical endpoints and corticosteroid sensitivity without any deterioration in pulmonary function. FENO and blood eosinophil number were reduced by HFA-BDP MDI ETN treatment. The visualization study suggested that ETN at expiratory flow rates of 10-30 L/min led to fine particle deposition in the middle meatus, including the sinus ostia. Co-incubation of eosinophils with BEAS-2B cells induced corticosteroid resistance. Conclusions: Additional HFA-BDP MDI ETN treatment was beneficial in patients with ECRS and should be considered as a potential therapeutic option for eosinophilic airway inflammation such as ECRS with asthma. (UMIN-CTR: R000019325) (http://www.umin.ac.jp/ctr/index.htm).

[A multicenter, open-label, randomized comparison of suppressive effects on asthmatic inflammation of lower airways and improved effects on health-related QOL between HFA-BDP and fluticasone propionate].

PURPOSE: It is important to evaluate the effects of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP), which shows predominant deposition in the lower airways, on asthmatic inflammation in the lower airways and the Quality of Life (QOL) of asthma patients, as compared with those of fluticasone propionate (FP) Diskus. METHODS: Seventy-seven adult patients with mild persistent or more severe asthma who were being treated with FP for >/=3 months were randomly assigned to the HFA-BDP group and continued FP group. The differential count of eosinophils in the peripheral blood, the serum cortisol levels, and pulmonary function parameters were measured before the study and at 3 months after the start of the study treatment. The improvements in the Asthma Quality of Life Questionnaire (AQLQ) scores were also compared. Sputum samples collected by the induced expectoration method (inhalation of 10% saline for 15 min) were divided into the early-phase sputum samples obtained within 15 minutes of the inhalation and the late-phase sputum samples obtained later than 15 minutes after the inhalation, and the eosinophil count and eosinophil cationic protein (ECP) levels were measured. RESULTS: In the HFA-BDP group (N=40), the differential count of eosinophils in the peripheral blood was significantly decreased as compared with that in the FP group (p=0.009), and the scores in all the domains of the AQLQ and the percentage improvement of the total score were significantly better as compared with those in FP group (p=0.033). The eosinophil count in the late-phase sputum samples (p=0.022) as well as the ECP level in the sputum samples showed more pronounced decreases in the HFA-BDP group as compared with those in the FP group. On the other hand, no significant changes were detected in the pulmonary function values. CONCLUSION: Use of the HFA-BDP preparation can more effectively suppress residual inflammation in the lower airways and significantly improve the QOL as compared with use of the FP preparation of asthma patients. Examination of induced sputum samples allows detection of changes in the peripheral airways that cannot be detected by pulmonary function testing.

Radiographic Evidence of Sinonasal Inflammation in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: An Underrecognized Association.

BACKGROUND: Sinonasal inflammation on both clinical examinations and imaging significantly impacts both asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to examine the association between sinonasal inflammation and asthma-COPD overlap syndrome (ACOS). METHODS: A total of 112 patients with a ratio of forced expiratory volume in 1 s to forced vital capacity of less than 70% were enrolled. COPD, asthma, and ACOS were clinically diagnosed according to the 2014 Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Sinonasal inflammatory condition was evaluated using sinus computed tomography, and its severity was assessed according to the Lund-Mackay staging (LMS) system. Ethmoid sinus-dominant shadow was defined as the presence of greater LMS scores for the anterior and posterior ethmoid sinuses than for the maxillary sinus. RESULTS: COPD, asthma, and ACOS were diagnosed in 55 (49.1%), 39 (34.8%), and 18 patients (16.1%), respectively. The frequency of radiographic evidence of sinonasal inflammation in patients with COPD, asthma, ACOS was 60.0%, 94.9%, and 72.2%, respectively. Patients with ACOS and COPD had only mild radiographic evidence of sinonasal inflammation (LMS score, 1-7), whereas moderate (LMS score, 8-11) and severe (LMS score, ≥12) radiographic evidence of sinonasal inflammation were detected only in patients with asthma. Furthermore, the frequency of ethmoid sinus-dominant shadow was significantly higher in patients with asthma than in those with COPD and ACOS. CONCLUSIONS: Radiographic evidence of sinonasal inflammation was a common comorbidity in ACOS. Future studies are required to examine the role of sinonasal inflammation in ACOS.

[Two cases of nemaline myopathy diagnosed after episodes of respiratory failure].

Here we report two cases of congenital myopathy visited our hospital with respiratory failure. Case 1 was a 31-year-old woman, who had muscular weakness from birth but had never been diagnosed. She had an onset of pneumonia followed by severe type 2 respiratory failure. Even after the healing of pneumonia, hypercapnia remained. A diagnosis of nemaline myopathy was made after muscle biopsy. Case 2 is a 62-year-old man, who had slowly progressing respiratory failure accompanied with severe hypercapnea. His respiratory failure was improved by NIPPV. He also under went muscle biopsy and nemaline myopathy was diagnosed. Nemaline myopathy is one of congenital myopathy and is known to be a nonprogressive or slowly progressive disorder. However, some patients are diagnosed appropriately only when adult onset acute respiratory failure occurs.

[A case of successful medical treatment for necrotizing fasciitis of the chest wall with diabetic nephropathy].

A 52-year-old man was given a diagnosis of type 2 diabetes mellitus at age 39. At age 46, he stopped taking medication. Two weeks after burning his legs at low temperature, he fell, using his right arm to protect his legs. The next day, he complained of pain and slight swelling from his right shoulder to his anterior chest and came to our hospital. At that time, a plain computed tomography scan suggested gasogenic bacterial infection and we discussed the indications for debridment. Although his widespread inflammation required extensive treatment including thoracostomy, we abandoned surgical treatment and administered several antibiotics in appropriate combination because of his severe condition. After admission, the mass grew rapidly and it was diagnosed as necrotizing fasciitis based on percutaneous needle biopsy and clinical findings. Although both inflammatory reactions and mass size tended to improve, he had repeated recurrence of pain and swelling in his right anterior chest. When he had a second recurrence, he received additional short-term steroid therapy. Afterwards he had no further recurrence. In this case, early clinical diagnosis, using broad-spectrum antibiotics prior to definite diagnosis, and additional short-term steroid therapy at the time of the recurrence were effective.

[Bronchial biopsy in allergic bronchopulmonary aspergillosis without clinical asthma].

A 24-year-old man who had had bronchial asthma between the ages of 10 and 12 years was admitted to our hospital on October 10, 2000. In May 1999, he had received antituberculosis therapy for left upper lobe infiltrate, which resolved two months later. Chest radiography on admission showed recurrence of the left upper lobe infiltrate. He complained of cough and low grade fever. Thoracic CT demonstrated gloved-finger shadows in the left upper lung field, as well as central bronchiectasis. Wheeze was not ausculated, and flow volume curve revealed no obstructive changes. Total IgE was markedly increased (6,084 IU/ml), and IgE RAST was positive for multiple allergens including Aspergillus species and precipitating antibody test against Aspergillus fumigatus was also positive. Bronchofiberscopy revealed mucoid impaction at the left B1 + 2, and culture of lavage fluid demonstrated Aspergillus fumigatus. A bronchial biopsy at the orifice of the left upper lobe bronchus revealed thickening of the basement membrane, eosinophil infiltration, and marked hypertrophy of the mucus glands. The diagnosis was allergic bronchopulmonary aspergillosis (ABPA), and 30 mg prednisolone was initiated and tapered. The infiltrate detected on chest radiography was resolved. Eight months later, asthmatic symptoms were observed, and Fluticasone dipropionate administration was started. However, the infiltration seen in the chest radiographs have not recurred until now. Asthmatic inflammation of the bronchial mucosa was demonstrated in a case of ABPA without clinical asthma.

[Serum rheumatoid factor and peripheral blood eosinophil counts in patients with bronchial asthma].

These days some reports say that bronchial asthma, especially severe asthma, is systemic inflammatory and its severity correlates with eosinophil counts. Some patients with asthma have positive tests for rheumatoid factor (RF) which is detected in systemic hyper immunoreactive desease such as rheumatoid arthritis. So we investigated each of these factors in asthmatic patients. We randomly selected 100 asthmatics from regular outpatients of our hospital. In a positive RF level group (over 21 IU/ml), Eosinophil counts were significantly higher than those in a negative RF level group. RF levels were significantly and positively correlated with the logarithm of eosinophil count. And in severe groups (patients with severe asthma, treated with high dose inhaled steroids, and with history of systemic steroids use for the last one month), RF levels were significantly higher than those in other groups. Our result suggested that RF levels reflect eosinophilia and asthma severity.