Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia.

PURPOSE: Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP. METHODS: IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis. RESULTS: The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP. CONCLUSIONS: Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia.

PURPOSE: Galectin-9 (Gal-9) is a ß-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS: Gal-9, transforming growth factor-ß1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS: Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.

Increased levels of plasma galectin-9 in patients with influenza virus infection.

Galectin-9 (Gal-9) is a ß-galactoside-binding protein involved in various biologic processes, including cell aggregation, adhesion, chemoattraction, and apoptosis. Little is known, however, about the regulation mechanisms of Gal-9 production. Recent studies reported high plasma Gal-9 levels in humans infected with human immunodeficiency virus-1 and dengue virus. Viral respiratory infections such as influenza are common human illnesses. A synthetic double-stranded RNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types and induces the expression of Gal-9 in endothelial cells. To examine the potential link between viral infection and Gal-9 expression, we measured plasma Gal-9 concentrations in patients with influenza. Subjects were 43 patients with influenza virus infection, 20 with pneumococcal pneumonia, and 20 healthy adults. Gal-9 concentrations in the plasma and in culture supernatants of human airway epithelial cells were measured using an enzyme-linked immunosorbent assay. Plasma Gal-9 concentrations were higher in patients with influenza infection than in patients with pneumococcal pneumonia and healthy subjects (p < 0.05). Patients with influenza were effectively differentiated from those with pneumococcal pneumonia or healthy subjects, based on the plasma levels of Gal-9 (p < 0.0001). Furthermore, using a human airway epithelial cell line, we showed that the presence of PolyIC but not lipopolysaccharides increased the Gal-9 concentration in the culture medium (p < 0.05), suggesting that PolyIC enhanced Gal-9 production. These findings support our proposal that Gal-9 production is induced by influenza virus infection in humans. In conclusion, plasma Gal-9 could be a new biomarker for patients with influenza infection.

Preventive effect of galectin-9 on double-stranded RNA-induced airway hyperresponsiveness in an exacerbation model of mite antigen-induced asthma in mice.

BACKGROUND: Viral respiratory infection is the most common cause of acute asthma exacerbation in patients with stable asthma. The replication of most respiratory viruses requires the generation of double-stranded RNA (dsRNA), resulting in the activation of host immune responses. Synthetic dsRNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types. To evaluate new therapies for mite antigen-induced chronic asthma, we developed an acute exacerbation model of mouse chronic asthma using mite antigen and PolyIC. We also examined the preventive effects of recombinant galectin-9 (Gal-9) on acute asthma exacerbation in this model. METHODS: Airway hyperresponsiveness (AHR) was examined to evaluate the exacerbation of chronic asthma. To analyze airway inflammation, the numbers of inflammatory cells and concentrations of cytokines in the bronchoalveolar lavage fluid (BALF) were estimated by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: AHR was accelerated by intranasal administration of PolyIC in addition to mite antigen. Levels of cytokines that contribute to AHR, including interferon-γ, tumor necrosis factor-α, and RANTES (CCR5), and of Gal-9 in the BALF were elevated in this acute asthma exacerbation mouse model. Intranasal administration of recombinant Gal-9 reduced the PolyIC-induced AHR and levels of these cytokines in the BALF. Further, Gal-9 suppressed the production of cytokines induced by PolyIC in the alveolar macrophages. CONCLUSIONS. Our findings demonstrated that exogenous Gal-9 suppressed dsRNA-induced AHR in an acute exacerbation model of chronic asthma in mice, and suggest that recombinant Gal-9 could be therapeutically effective for preventing acute asthma exacerbation.

Clinical analysis of patients with pulmonary nontuberculous mycobacterial disease complicated by pneumothorax.

OBJECTIVE: We clarified the clinical characteristics of patients with pulmonary nontuberculous mycobacterial (NTM) disease complicated by pneumothorax. METHODS: We retrospectively selected 220 patients who satisfied the diagnostic criteria for NTM disease proposed by the American Thoracic Society (ATS). Nine patients with pulmonary NTM disease were complicated with pneumothorax. We investigated the patients' background, laboratory findings, radiological findings, treatment and prognoses. RESULTS: There were nine patients, including six men and three women, with a mean age of 73.2 years. Seven patients had underlying respiratory diseases such as chronic obstructive pulmonary disease (COPD) excluding pulmonary NTM disease. The causative microorganisms was Mycobacterium avium in four patients, M. intracellulare in four patients, and M. kansasii in one patient. Regarding the radiological findings, pneumothorax was recognized in the right lung in five patients, in the left lung in three patients, and in both lungs heterogeneously in one patient. Although most patients exhibited multiple cavities and extensive lesions over the unilateral lung fields, three patients were simultaneously diagnosed with pulmonary NTM disease at the onset of pneumothorax. As for treatment, thoracic drainage was performed in seven patients, while one patient was advised only to rest and one patient required both thoracic drainage and surgery. The responses to the treatment was poor in each case, and five patients died due to pneumonia or heart failure. CONCLUSION: In this study, the rate of pneumothorax complications in the patients with pulmonary NTM disease (4.1%) was higher than that of other reports. The responses to treatment, and prognoses were poor due to the presence of other complications.

Critical role of interleukin-5 in the development of a mite antigen-induced chronic bronchial asthma model.

OBJECTIVE AND DESIGN: Asthma is associated with eosinophilic airway inflammation and characterized by enhanced airway sensitivity. Interleukin (IL)-5 plays an important role in the pathogenesis of asthma. The involvement of IL-5 receptor-mediated cellular signals in the pathogenesis of a mite antigen-induced chronic asthma model was investigated. SUBJECTS: In this study, 48 female C57BL/6J (WT) mice and IL-5 receptor-deficient (IL-5RKO) mice were used. TREATMENT: Mite antigen (50 µl) was intranasally administered 13 times to WT and IL-5RKO mice. METHODS: Airway hypersensitivity (Mch PC200) and specific antigen exposure tests were performed, and lung tissue, bronchoalveolar lavage fluid (BALF), and blood were collected to investigate the asthma pathology and differences in the local pulmonary levels of cytokines and chemokines. RESULTS: Airway sensitivity was enhanced and antigen-specific airway resistance was increased in WT mice. In addition, the number of eosinophils and Th2 cytokine levels in the BALF were increased. In contrast, IL-5RKO mice did not acquire the asthma pathology, such as antigen-specific airway resistance and eosinophilic airway inflammation. Mch PC200 was significantly correlated with cysteinyl leukotriene levels in WT mice. CONCLUSION: These findings suggested that both IL-5 induced eosinophils and cysteinyl leukotrienes are involved in the pathology of this mite antigen-induced chronic asthma model.

Mucoid impaction of the bronchi caused by Mycobacterium avium.

A 25-year-old woman with a past history of congenital adrenal cortex hypertrophy visited our hospital complaining of a continuous cough. On chest CT, a localized bronchiectatic lesion was recognized with mucoid impaction in the right lower lobe. Because we obtained a positive smear test for acid-fast bacilli and polymerase chain reaction (PCR) of the bronchoscopic specimens was positive for M. avium, we administered combined chemotherapy; however, the clinical effect was poor and video-assisted thoracoscopic surgery (VATS) was performed. As the histological findings revealed a granuloma with caseating necrosis and mucous plugs containing M. avium in the respiratory bronchioles, we diagnosed the patient with mucoid impaction of the bronchi (MIB) due to M. avium.

Step-down of budesonide/formoterol in early stages of asthma treatment leads to insufficient anti-inflammatory effect.

OBJECTIVE: Administration of the combination of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is the main treatment strategy for bronchial asthma. The ICS/LABA dosage can be reduced (stepped down) when the patient's symptoms and lung functions are well-controlled. In this study, we obtained fractional exhaled nitric oxide (FeNO) measurements to clarify whether the anti-inflammatory effect of budesonide/formoterol is shortened by step-down. METHODS: Fifty-four patients who visited the Kawasaki Medical School Hospital with newly diagnosed asthma from November 2008 to July 2010 received budesonide/formoterol for 8 weeks or more. In 29 patients, the forced expiratory volume in 1 s% predicted increased to 80% or more, and the Asthma Control Questionnaire (ACQ) score decreased to 0.5 or less within 12 weeks. These 29 patients were randomly divided into two groups: the dosage-continued group (n = 14) and the step-down group (n = 15). Then, the impact of budesonide/formoterol step-down on ACQ score, pulmonary function and FeNO level was compared between the groups. RESULTS: In the step-down group, the dosage was stepped down from 538 mcg/day to 331 mcg/day. In both groups, pulmonary function indicators and symptoms did not change. However, the mean FeNO level decreased significantly in the dosage-continued group (from 50.9 ppb to 45.0 ppb), and increased significantly in the step-down group (from 51.0 ppb to 65.7 ppb). CONCLUSIONS: Clinicians should be more careful when stepping down budesonide/formoterol based solely on patients' symptoms and/or pulmonary function.

Serological assay by use of glycopeptidolipid core antigen for Mycobacterium avium complex.

OBJECTIVE: We evaluated the clinical usefulness of glycopeptidolipid (GPL) core antigen for diagnosing Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD), including patients with clinically suspected MAC-PD. METHODS: GPL core antibody levels were measured in 57 patients with MAC-PD satisfying the American Thoracic Society (ATS) criteria for pulmonary disease due to non-tuberculous mycobacteria (NTM), and in 18 patients with clinically suspected MAC-PD, 10 with MAC contamination, 18 with pulmonary tuberculosis (TB), 9 with other NTM disease, 18 with other lung diseases, and 20 healthy subjects. RESULTS: The positive response rate was 77% for MAC-PD, 39% for suspected MAC-PD, 10% for MAC contamination, and 0% for pulmonary TB, other NTM diseases, other lung diseases, and healthy subjects. GPL core antibody levels were significantly higher in patients with MAC-PD than in those of the other groups (p < 0.01). The sensitivity and specificity of the GPL core antibody assay for MAC were 77% and 99%, respectively. Among 13 patients with MAC-PD who showed false-negative results, 5 had immunosuppressive underlying diseases. No significant correlations between the antibody level and species of MAC, clinical disease types, and extent of the disease on chest computed tomography were found in patients with MAC-PD. CONCLUSION: This enzyme immunoassay kit is a useful supportive method for the rapid and convenient diagnosis of MAC-PD using a small dose of serum, and for the differentiation of MAC-PD from other lung diseases. However, underlying diseases need to be considered in the interpretation of negative results.

Pulmonary Mycobacterium kyorinense disease showed clinical improvement following combined therapy with clarithromycin and levofloxacin.

A 63-year-old man with a past history of resection of pulmonary adenocarcinoma and COPD visited our hospital because of fever, cough and purulent sputum. Chest CT showed an infiltration shadow with multiple bullae in the right lung. There was a slight elevation of the inflammatory response. We established a definitive diagnosis by frequent isolation of Mycobacterium kyorinense on a sputum culture test of acid-fast bacilli. Clarithromycin and levofloxacin were administered after identification of M. kyorinense using a 16S rRNA gene sequence. Subsequently his symptoms improved following combined therapy with clarithromycin and levofloxacin.

Usefulness of tuberculin skin test and three interferon-gamma release assays for the differential diagnosis of pulmonary tuberculosis.

BACKGROUND: We compared the usefulness of tuberculin skin test (TST) and three interferon-gamma release assays (IGRAs) [QuantiFERON-TB Gold (QFT-2G), QuantiFERON-TB Gold In-tube (QFT-3G), T-SPOT.TB] as the supportive method for diagnosing pulmonary tuberculosis (TB). METHODS: The subjects were 66 patients who required clinical differentiation of pulmonary TB. The final clinical diagnosis of pulmonary TB in 22 patients and non-pulmonary TB in 44 patients was established by clinical specimens. RESULTS: In 22 patients with pulmonary TB, the positive response rate was 59.1% on TST, 81.8% on QFT-2G, 86.4% on QFT-3G and 95.5% on T-SPOT.TB. In 44 patients with non-pulmonary TB disease, the positive response rate was 40.9% on TST, 6.8% on QFT-2G, 6.8% on QFT-3G, 13.6% on T-SPOT.TB. Indeterminate results on three IGRAs were recognized in one patient each on QFT-2G and QFT-3G among patients with pulmonary TB and in two patients each on QFT-2G and QFT-3G among patients with non-pulmonary TB. However, there were no indeterminate results on T-SPOT.TB in either patient group. Patients with false-negative or indeterminate results on IGRAs had severe underlying diseases or were receiving immunosuppressive treatments. CONCLUSION: There were no significant differences among the three IGRA tests in this study. However, because the three IGRA tests showed a significantly higher positive response rate for patients with pulmonary TB and a lower positive response rate for patients with non-pulmonary TB than TST, the three IGRA tests seemed to be more useful than TST for the differentiation of patients with pulmonary TB.

Relationship between clinical efficacy for pulmonary MAC and drug-sensitivity test for isolated MAC in a recent 6-year period.

There are a few recent reports about the relationship between the clinical effect and drug-sensitivity test. We investigated the relationship between the clinical efficacy of treatment for pulmonary Mycobacterium avium complex (MAC) and drug-sensitivity test for isolated MAC by comparison between data from 2005 to 2007 and from 2008 to 2010. We studied 60 patients who satisfied diagnostic criteria of nontuberculous mycobacterial infection established by the American Thoracic Society in 2007 and who received combination therapy using rifampicin (RFP), ethambutol (EB), streptomycin (SM), and clarithromycin (CAM). Average CAM dosage was increased from the early (517 mg/day) to the later (800 mg/day) period. Sputum conversion rate increased from 63% in the early period to 83% in the later period. Clinical improvement also increased from 38% in the early period to 53% in the later period. The causative microorganisms isolated were M. avium in 35 patients and M. intracellulare in 25. In both periods, isolated MAC strains showed excellent minimum inhibitory concentration (MIC) for CAM. Regarding the relationship between clinical efficacy and MICs of RFP, EB, CAM, and SM, most patients with good clinical effects showed low MIC for CAM in both periods. Good clinical efficacy, including the sputum conversion rate, was obtained with an increased dose of CAM in the later period. We speculate that the increased dose of CAM influenced the good clinical effect in both periods.

Pulmonary Mycobacterium massiliense disease with septicemia during immunosuppressive treatment.

A 75-year-old man with interstitial pneumonia due to ANCA-related vasculitis requiring immunosuppressive treatment was admitted to our hospital because of fever and rapidly progressive dyspnea. Chest CT showed diffuse ground-glass opacity with infiltration shadow in the bilateral lungs. We established a definitive diagnosis by isolating Mycobacterium massiliense on culture examination of acid-fast bacilli from peripheral blood and sputum. We began to administer CAM, LVFX, AMK, IPM/CS to this patient two weeks after admission. However, he died of respiratory failure and septic shock. There are few case reports of pulmonary lesion with septicemia due to Mycobacterium massiliense.

Stability of sealed-bag samples for off-line measurement of fractional exhaled nitric oxide.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measurement is an index of airway eosinophilic inflammation and is primarily employed to diagnose bronchial asthma and assess airway inflammation. It can be measured with on- and off-line methods. In the latter, sample storage is possible; this is useful in Japan, because the number of facilities in which this instrument has been installed is limited. OBJECTIVE: We investigated the maximum period in which the samples continued to show stable values, as well as the influences of the storage environment. METHODS: Exhaled air samples were collected from 19 bronchial asthma patients (male/female: 8/11; mean age: 54.9 ± 15.6 years), and divided into 2 groups: a group with an FeNO level of less than 30 ppb and that with a level of 30 ppb or more. They were stored at 4 and 25°C to examine serial changes. RESULTS: The off-line-measured FeNO value was 33.7 ± 17.1 ppb, significantly lower than the on-line measured value (71.4 ± 47.7 ppb) (P < .01). In a group with an FeNO level of less than 30 ppb, temperature had no influence. However, in the other group, the period was prolonged to 72 hours when the samples were stored at 4°C. The samples were stable at 4°C for 24 hours, regardless of the initial measurements. CONCLUSION: The duration of sample storage can be prolonged at 4°C. The standard FeNO measurement method is the on-line method, but the alternative use of the off-line method may contribute to the diagnosis and treatment of the patients.

[Usefulness of fractional exhaled nitric oxide measurement for cough treatment].

Cough is a frequent chief complaint of outpatients, and is caused by various diseases. Fractional exhaled nitric oxide (FeNO) measurement is employed to evaluate airway eosinophilic inflammation. We investigated the usefulness of FeNO measurement for the differentiation of diseases in 202 patients who consulted our department. The numbers of consultations required to determine the therapeutic strategy were compared between before and after the introduction of FeNO measurement. The numbers of consultations before treatment were 2.00 +/- 1.31 (n = 140) and 1.60 +/- 0.65 (n = 62) before and after FeNO measurement, respectively (p = 0.046). In patients with cough variant asthma or bronchial asthma, the numbers were 2.15 +/- 1.60 and 1.40 +/- 0.67 before and after FeNO measurement, respectively (p = 0.003). FeNO measurement may be useful for cough treatment.

Solitary pulmonary nodule due to Mycobacterium kansasii.

A 46-year-old man with no past history of underlying disease was admitted to our hospital for examination of abnormal chest shadow on chest radiograph. He had no respiratory symptoms on admission. Chest radiograph showed a solitary nodule (35 × 20 mm) in the left upper lung field. On chest CT, this nodule in the left upper lobe (S(1+2)) did not demonstrate calcification, the margin was clear but irregular, and there was pleural indentation. The solitary nodule was strongly positive on PET/CT. Therefore, we suspected primary lung cancer. Because we could not establish the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery (VATS) was performed. Histological diagnosis of the solitary nodule demonstrated epitheloid granuloma with caseous necrosis. Smear test of the resected tissue was positive for acid-fast bacilli and culture was positive for mycobacteria, which was identified as Mycobacterium kansasii. There are a few case reports of solitary nodule due to M. kansasii.

Impaired coronary flow reserve in obstructive sleep apnea and its improvement after continuous positive airway pressure therapy: a transthoracic Doppler echocardiographic study.

BACKGROUND: It is reported that patients with obstructive sleep apnea syndrome (OSAS) show endothelial dysfunction and that treatment of OSAS by continuous positive airway pressure (CPAP) therapy improves it. OBJECTIVE: In this study we evaluated coronary flow reserve (CFR), which is considered to be affected by coronary microvascular dysfunction, and the change in CFR during treatment of OSAS by CPAP. METHODS: Eleven patients who were diagnosed as having OSAS by polysomnography (PSG) were studied. Phasic coronary flow velocity was obtained in the left anterior descending coronary artery at baseline and during hyperemic conditions with transthoracic 2D echocardiography. CFR was defined as the ratio of hyperemic to basal mean diastolic velocity. CFR was obtained before and after the initiation of CPAP therapy. RESULTS: Coronary flow reserve was decreased (<2.5) in 8 of 11 (73%) patients at baseline. After CPAP therapy, CFR of these 8 patients increased significantly. CONCLUSION: Coronary flow reserve was decreased in 73% of the patients with OSAS and was significantly improved after CPAP therapy.

Nutritional deficits in elderly smokers with respiratory symptoms that do not fulfill the criteria for COPD.

BACKGROUND AND OBJECTIVE: Whereas nutrition deficits are recognized as an expression of systemic inflammation in the elderly with diagnosed chronic obstructive pulmonary disease (COPD), if they occur in symptomatic elderly smokers, unfulfilled COPD criteria are not confirmed. METHODS: Respiratory function, anthropometry assessment, and diet intake evaluation of 13 COPD patients (COPD group), ten symptomatic elderly smokers (SYSM group), and 27 healthy volunteers (control group) were compared. All were 70 years old or older. RESULTS: The SYSM group had lower body weight, body mass index, percentage ideal body weight, body fat percentage, arm muscle circumference, tricep skin fold thickness, serum albumin, prealbumin, and transferrin than the control group and were similar to the COPD group (P < 0.05 each and nonsignificant each). Resting energy expenditure was no different among the groups. Intake of energy, vitamins (A, B1, B2, and C), calcium, iron, fiber, and sodium was also lower in the SYSM group than in the control group (P < 0.05 all) and was similar to the COPD group. CONCLUSION: Elderly smokers who are symptomatic but who do not fulfill the COPD diagnostic criteria have nutritional deficits related to insufficient energy intake that are similar to those seen in COPD patients.

Clinical usefulness of combination chemotherapy for pulmonary Mycobacterium avium complex disease.

BACKGROUND: This study compared the clinical usefulness of combination chemotherapy including various doses of clarithromycin (CAM) for pulmonary Mycobacterium avium complex (MAC) disease. METHODS: The subjects were divided into three groups receiving combination chemotherapy at various dose levels of CAM. The analysis of microbiological effects was based on the sputum conversion rate and sputum relapsing rate and that of clinical effects was performed by clinical symptoms and radiological findings for patients with pulmonary MAC disease. RESULTS: There were no significant differences among the three groups with regard to patient characteristics. The sputum conversion rate significantly increased with the dose of CAM (CAM 400mg: 43%, CAM 600mg: 69%, CAM 800mg: 88%). The sputum relapsing rate did not significantly differ among the three groups (CAM 400mg: 47%, CAM 600mg: 35%, CAM 800mg: 33%). Along with the sputum conversion rate, the rate of clinical improvement was significantly increased with the dose of CAM (CAM 400mg: 27%, CAM 600mg: 40%, CAM 800mg: 54%). Adverse reactions, such as gastrointestinal symptoms, were most frequently recognized in the group receiving CAM 800mg (38%) compared to those in the other two groups (CAM 400mg: 23% and CAM 600mg: 25%). CONCLUSIONS: Although both the sputum conversion rate and clinical improvement significantly increased with the dose of CAM, the rate of adverse reactions, such as gastrointestinal symptoms, also increased. It is important to continue close monitoring of patients with pulmonary MAC disease treated with a regimen that includes CAM 800mg.