The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

BACKGROUND: Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. METHODS: In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. RESULTS: A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. CONCLUSIONS: A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.

The therapeutic effects of bronchial thermoplasty evaluated by cardiopulmonary exercise testing†:†a case series.

Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma. We evaluated the therapeutic effects of BT using cardiopulmonary exercise testing (CPET). After BT, the exercise time during CPET substantially prolonged reducing exertional dyspnea in the former (good), but not in the latter (poor). In the good responder, the high air remaining in the lung after expiration (i.e., inspiratory tidal volume minus expiratory tidal volume) during CPET decreased after BT. In contrast, in the poor responder, the high air remaining after expiration during exercise was not obtained before BT. Further investigations are necessary to confirm that the presence or absence of the exertional wasted ventilation on CPET may be informative to evaluate the therapeutic effects of BT. J. Med. Invest. 67 : 386-390, August, 2020.

Evaluation of disease severity in bronchiectasis using impulse oscillometry.

Although the diagnostic value of impulse oscillometry (IOS) in bronchiectasis for the differential diagnosis of healthy subjects has been researched, the usefulness of each IOS parameter for predicting disease severity in bronchiectasis has not been thoroughly investigated. In addition, the usefulness of IOS in patients with nontuberculous mycobacteria (NTM) infection has not been reported. This study aimed to determine the predictive significance of respiratory impedance and detect the other most significant IOS parameters for predicting disease severity in bronchiectasis patients and to validate the usefulness of IOS in patients with NTM infection. A total of 206 patients with bronchiectasis who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center were included. Chest high-resolution computed tomography, spirometry and IOS were performed. Hospital admissions, mortality and disease severity indices for bronchiectasis (Bronchiectasis Severity Index (BSI), FACED, and E-FACED scores) were calculated to assess disease severity. The patients were divided into subgroups with and without NTM infection, and subgroup analyses were performed. Respiratory reactance, especially resonant frequency (f res), correlated with both BSI and FACED score better than respiratory resistance. Inspiratory but not expiratory impedance was strongly correlated with BSI, FACED and E-FACED scores. Inspiratory f res was the most useful predictor, increasing as the disease became more severe. The usefulness of IOS was almost equivalent in patients both with and without NTM infection. Inspiratory reactance measured by IOS is useful for estimating disease severity in bronchiectasis. Inspiratory f res best predicts disease severity in bronchiectasis patients both with and without NTM infection.

Intolerance to and limitations of inspiratory muscle training in patients with advanced chronic obstructive pulmonary disease: A report of two cases.

Inspiratory muscle training (IMT) has been attracting attention as one of the useful treatments in patients with chronic obstructive pulmonary disease (COPD). IMT is reportedly effective in most patients with COPD. However, little is known about the benefits of IMT, especially in patients with advanced COPD. We reported two cases of COPD that received 12-week IMT to explore intolerance to and the limitations of IMT in advanced COPD. The effectiveness of IMT was evaluated using cardiopulmonary exercise testing (CPET), spirometry, and respiratory muscle strength testing before and after the training. A 75-year-old man with normal body mass index (BMI) and forced expiratory volume in 1 s (FEV1) of 1.63 L responded well to IMT, but a 78-year-old man with low BMI and FEV1 of 0.83 L did not. In the responder, IMT resulted in increased minute ventilation (V' E) and oxygen uptake at peak exercise in incremental load testing. Moreover, IMT increased endurance time in constant load testing and maximal inspiratory pressure. In both patients, breathing frequency (f R) increased, but tidal volume and the inspiratory-expiratory ratio were not improved during exercise. Despite the high f R obtained after IMT, V' E at peak exercise did not increase and endurance time shortened in the non-responder. In underweight patients with advanced COPD, IMT might lead to tachypnea and ventilatory inefficiency, which in turn might decrease exercise performance. Therefore, underweight patients with advanced COPD might be unable to tolerate IMT and should avoid receiving the training.

Managing COPD with expiratory or inspiratory pressure load training based on a prolonged expiration pattern.

BACKGROUND: Exertional prolonged expiration should be identified as a therapeutic target in COPD. The efficacy of expiratory or inspiratory pressure load training (EPT/IPT) based on the degree of prolonged expiration was investigated. METHODS: A total of 21 patients with COPD were divided into two groups according to the exertional change in the inspiratory duty cycle (T I/Ttot). For 12 weeks, patients whose exertional T I/Ttot decreased received EPT (EPT group, n=11, mean percentage forced expiratory volume in 1 s (%FEV1), 32.8%) and those whose exertional T I/Ttot increased received IPT (IPT group, n=10, mean %FEV1, 45.1%). RESULTS: The therapeutic responses were as follows. In both groups, endurance time (EPT, +5.7 min, p<0.0001; IPT, +6.1 min, p=0.0004) on the constant work rate exercise test (WRET) and peak oxygen uptake increased (EPT, p=0.0028; IPT, p=0.0072). In the EPT group the following occurred: 1) soon after commencement of exercise with the constant WRET, the expiratory tidal volume (V Tex) increased, reducing dyspnoea; 2) V Tex and mean expiratory flow increased and then prolonged expiration (p=0.0001) improved at peak exercise with the incremental exercise test (ET); and 3) St. George's Respiratory Questionnaire total, activity and impact scores were improved. In the IPT group, on both the constant WRET and incremental ET, breathing frequency increased, which led to greater exercise performance with effort dyspnoea. CONCLUSIONS: This study showed the benefits of EPT/IPT on exercise performance. If the choice of managing COPD with EPT/IPT is appropriate, inexpensive EPT/IPT may become widespread as home-based training.

Diagnostic Validity of Gastric Aspirate Culture in Nontuberculous Mycobacterial Pulmonary Disease.

Rationale: Although gastric aspirate culture is used for diagnosing pulmonary tuberculosis, its usefulness in diagnosing pulmonary infections of nontuberculous mycobacteria (NTM) is unknown.Objectives: To investigate the diagnostic validity of gastric aspirate culture for acid-fast bacilli in NTM pulmonary disease (NTM-PD).Methods: Gastric aspirates were collected from patients with suspected NTM-PD at the Osaka Toneyama Medical Center between December 2006 and February 2018. Patients with a final diagnosis of pulmonary tuberculosis, an observation period of less than 6 months, or fewer than three conducted sputum cultures were excluded from the study. NTM-PD was diagnosed as per American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria. We retrospectively examined the diagnostic validity of gastric aspirate culture in Mycobacterium avium complex (MAC)-PD and M. kansasii-PD by comparing culture results with final diagnoses. This was done first for all patients, and subsequently for patients with negative results for early sputum cultures. In addition, we compared the time required for an NTM-PD diagnosis based on gastric aspiration with that based on ATS/IDSA criteria.Results: Among 475 total patients, 119 (25.1%) had positive NTM gastric aspirate cultures and 154 (32.4%) fulfilled the ATS/IDSA criteria for NTM-PD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) of gastric aspiration were 63.9%, 95.8%, 83.5%, and 88.8% in MAC-PD and 82.4%, 99.6%, 87.5%, and 99.3% in M. kansasii-PD, respectively. Sensitivity, specificity, PPV, and NPV of gastric aspirate cultures of the 378 patients who were undiagnosed based on sputum culture within 120 days were 34.0%, 95.5%, 51.6%, and 91.1% for MAC-PD and 75.0%, 99.5%, 60.0%, and 99.7% for M. kansasii-PD, respectively. Furthermore, gastric aspirate cultures tested in addition to bronchoscopy yielded incremental sensitivity of 8.7% (95.7% vs. 87.0%) and an NPV of 1.3% (99.3% vs. 98.0%) in MAC-PD. In patients with NTM-PD with NTM-positive gastric aspirate cultures, the period between gastric aspirate collection and the positive culture result was shorter than the time between gastric aspirate collection and NTM-PD diagnosis (6 [9-36] d vs. 25 [12-69] d, median [interquartile range], P < 0.0001].Conclusions: In settings where acid-fast bacilli pulmonary diseases are suspected, gastric aspirate culture may be helpful for diagnosing MAC-PD and M. kansasii-PD.

Evaluation of Exertional Ventilatory Parameters Using Oscillometry in COPD.

Background: Oscillometry is a tool to measure respiratory impedance that requires minimal patients' effort. In patients with chronic obstructive pulmonary disease (COPD), the correlation of respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported. In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated. The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD. Methods: Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks. The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman's rank correlation coefficient, univariate, and multivariate analyses. Results: Respiratory reactance had better correlations with the CPET parameters than respiratory resistance. Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance. In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (rS=-0.549, p<0.01) and dead space to tidal volume ratio at peak exercise (rS=0.677, p<0.01) and the best predicted expiratory tidal volume (VT ex) at peak exercise of all the oscillometric parameters (rS=-0.679, p<0.01). However, the correlation between Fres-ins and VT ex at peak exercise became weak in subjects with severe and very severe COPD during exercise. Conclusion: Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD. The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome.

BACKGROUND: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection. METHODS: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease. RESULTS: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence. CONCLUSIONS: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

Long-Term Treatment Outcome of Progressive Mycobacterium Avium Complex Pulmonary Disease.

BACKGROUND: Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. METHODS: We retrospectively evaluated the clinical characteristics and long-term outcomes in patients with chemo-naïve progressive MAC-PD, hospitalized for first-line multidrug therapy. RESULTS: Among 125 patients, 86 (68.8%) received standardized treatment (rifampicin, ethambutol, clarithromycin), 25 (20.0%) received a fluoroquinolone (FQ)-containing regimen, and 53 (42.4%) received aminoglycoside injection. The sputum conversion rate was 80.0%, and was independently associated with standardized treatment. The incidence of refractory disease (45.6%) was independently and negatively associated with standardized regimen and aminoglycoside use. Choice of an FQ-containing regimen was not associated with positive outcome. Clarithromycin resistance occurred in 16.8% and was independently associated with refractory disease. MAC-PD-associated death occurred in 3.3% of patients with non-cavitary nodular bronchiectasis (NB) and 21.3% with cavitary MAC-PD over a median follow-up period of 56.4 months. The rates of MAC-PD-associated death were comparable between cavitary-NB and fibrocavitary disease. Concurrent chronic pulmonary aspergillosis (CPA) occurred in 13 (17.3%) patients with cavitary MAC-PD, and age, diabetes mellitus, and CPA were independent risk factors for mortality. CONCLUSIONS: Standardized intensive multidrug treatment reduces disease progression and persistence in progressive MAC-PD. Cavitary NB may differ from, rather than being just an advanced stage of, non-cavitary NB. The high incidence and significant mortality of CPA in cavitary MAC-PD highlight the need for early diagnosis and treatment.

Influenza Vaccination-associated Acute Thrombocytopenia and Diffuse Alveolar Hemorrhage.

Influenza vaccination can trigger various adverse reactions, and thrombocytopenia is also rarely reported. Although patients with mild thrombocytopenia are sometimes asymptomatic, severe thrombocytopenia can cause severe bleeding. We herein report a rare case of severe thrombocytopenia that occurred within one day of influenza vaccination and diffuse alveolar hemorrhage (DAH) leading to acute respiratory failure. The patient was treated with glucocorticoid pulse therapy, intravenous immunoglobulin, and temporary mechanical ventilation, and eventually he made a full recovery. Vaccine-related thrombocytopenia and DAH should be considered adverse reactions, even if they develop very soon after vaccination.

Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease：A case report.

The presence of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is closely associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. Despite intensive immunosuppressive therapies, some of these patients still have a poor prognosis with few treatment options. Although removal of pathogenic autoantibodies and cytokines by plasma exchange (PE) could be a treatment option, its safety and efficacy have never been determined. We report a patient with anti-MDA5 Ab-positive RP-ILD who was refractory to intensive therapies including steroids, cyclosporine, and intravenous cyclophosphamide, and then treated by PE to prevent the progression of RP-ILD. Shortly after the initiation of PE therapy, however, his respiratory condition suddenly deteriorated due to acute pulmonary edema and the patient died on the following day. Transfusion-related acute lung injury (TRALI) would be the most likely cause of the acute pulmonary edema because there was no sign of circulatory overload. To the best of our knowledge, this is the first report showing a critical adverse event associated with PE therapy for these patients. This case supports the idea that the presence of ILD could increase a risk for TRALI and therefore we should carefully evaluate the eligibility for PE therapy of anti-MDA5 Ab-positive RP-ILD patients given the risk of acute lung injury. Further studies collecting more clinical data are necessary to assess the efficacy, safety, and risk factors of PE therapy for these patients.

Characteristic chest CT findings for progressive cavities in Mycobacterium avium complex pulmonary disease: a retrospective cohort study.

BACKGROUND: Although cavities are an important finding in Mycobacterium avium complex pulmonary disease (MAC-PD), there is little information regarding the types of cavities that indicate disease progression. This study was performed to identify cavity characteristics that were associated with disease progression in patients with MAC-PD. METHODS: This retrospective cohort study included 97 patients presenting with MAC-PD with cavities between December 2006 and June 2016. We compared initial and final computed tomography (CT) findings, classified 52 and 45 patients in the progressive and non-progressive cavity groups, respectively, and examined the progression-related imaging features in initial CT images. A progressive cavity was defined by more than two-fold increase in internal diameter or emergence of a new cavity around the initial cavity. RESULTS: Patients in the progressive group were older (p < 0.001), had a lower body mass index (p = 0.043), and showed higher diabetes complication rates (p = 0.005). The initial CT in the progressive group showed a longer maximum internal diameter of the cavity (p < 0.001) and higher rates of cavities close to the chest wall (p < 0.001), multiple cavities (p = 0.023), consolidation around the cavity (p < 0.001), atelectasis (p = 0.011), and pleural thickening (p < 0.001). Multivariable logistic regression analysis revealed that the maximum internal diameter of the cavity (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.02-1.21; p=0.012) and consolidation around the cavity (OR: 16.15, 95% CI: 4.05-64.46; p < 0.001) were significantly associated with progressive cavities. In cavities with a maximum internal diameter of ≥10 mm and simultaneous consolidation, the probability of progression was as high as 96.2%. The 10-year mortality rates in the progressive and non-progressive cavity groups were 46.7 and 9.8% (p < 0.001), respectively, while the 10-year respiratory failure rates were 28.1 and 0%, respectively (p < 0.001). CONCLUSIONS: Large cavity size and consolidation on CT showed strong relationships with disease progression, which led to respiratory failure and high mortality rate.

A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O2 pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O2 delivery through improvements in primary cardiocirculatory and muscular crosstalk.

Three Cases of Idiopathic Diffuse Pulmonary Ossification.

Diffuse pulmonary ossification (DPO) is an uncommon diffuse lung disease characterized by metaplastic bone formation in the lung parenchyma and is rarely diagnosed in life. While DPO usually occurs as a secondary disease, idiopathic cases are extremely rare. We describe three cases of idiopathic DPO, two of which were definitively diagnosed by surgical lung biopsy. One case was observed in a 43-year-old man with a history of recurrent pneumothorax who developed pneumothorax after the surgical biopsy. Few reports have described cases of DPO with recurrent pneumothorax; however, pneumothorax should be considered as a potential complication when such patients are encountered.

Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without significantly changing the resting pulmonary function in asthmatics. To understand the mechanism, cardiopulmonary variables were investigated using cardiopulmonary exercise testing (CPET) in a patient with severe asthma before and after BT. CASE PRESENTATION: A 57-year-old Japanese man visited our hospital for consultation of the intractable asthma, which we managed with three treatment sessions of BT. Comparison of the findings pre-BT and at 1 year after BT demonstrated that (1) the resting tests for respiration showed no improvement in forced expiratory volume in 1 s, but the forced oscillation technique showed decreases in both inhalation and exhalation respiratory resistance values, and (2) the CPET results showed (i) improvement in exertional dyspnea, exercise endurance, and arterial oxygen saturation at the end of exercise; (ii) that the expiratory tidal volume exceeded the inspiratory tidal volume during exercise, which implied that a sufficient exhalation enabled longer inspiratory time and adequate oxygen absorption; and (iii) that an increase in respiratory frequency could be prevented throughout exercise. CONCLUSIONS: This case report described a novel mechanism of BT in improving exertional dyspnea and exercise duration, which was brought about by ventilatory improvements related to the breathing pattern of inspiration to expiration.

Dyspnea and the Varying Pathophysiologic Manifestations of Chronic Obstructive Pulmonary Disease Evaluated by Cardiopulmonary Exercise Testing With Arterial Blood Analysis.

Background: Patients with chronic obstructive pulmonary disease (COPD) show varying mechanisms of exertional dyspnea with different exercise capacities. Methods: To investigate the pathophysiologic conditions related to exertional dyspnea, 294 COPD patients were evaluated using cardiopulmonary exercise testing (CPET) with arterial blood analyses, with the patients classified into two groups according to their exercise limitation: the leg fatigue group (n = 58) and the dyspnea group (n = 215). The dyspnea group was further subdivided into four groups based on peak oxygen uptake ( V ° O 2 in mL/min/kg): group A (< 11), group B (11 to < 15), group C (15 to < 21), and group D (≥21). Results: In the dyspnea group, group A (n = 28) showed the following findings: (i) the forced expiratory volume in 1 s was not correlated with the peak V ° O 2 (p = 0.288), (ii) the arterial oxygen tension (PaO2) slope (peak minus resting PaO2/Δ V ° O 2 ) was the steepest (p < 0.0001) among all subgroups, (iii) reduced tidal volume (VT) was negatively correlated with respiratory frequency at peak exercise (p < 0.0001), and (iv) a break point in exertional VT curve was determined in 17 (61%) patients in group A. In these patients, there was a significant negative correlation between bicarbonate ion ( HCO 3 - ) levels at peak exercise and VT level when the VT-break point occurred (p = 0.032). In group D (n = 46), HCO 3 - levels were negatively correlated with plasma lactate levels (p < 0.0001). In all subgroups, the HCO 3 - level was negatively correlated with minute ventilation. The dyspnea subgroups showed no significant differences in the overall mean pH [7.363 (SD 0.039)] and Borg scale scores [7.4 (SD, 2.3)] at peak exercise. Conclusions: During exercise, ventilation is stimulated to avoid arterial blood acidosis and hypoxemia, but ventilatory stimulation is restricted in the setting of reduced respiratory system ability. These conditions provoke the exertional dyspnea in COPD. Although symptom levels were similar, the exertional pathophysiologic conditions differed according to residual exercise performance; moreover, COPD patients showed great inter-individual variability. An adequate understanding of individual pathophysiologic conditions using CPET is essential for proper management of COPD patients.

Exercise tolerance and balance of inspiratory-to-expiratory muscle strength in relation to breathing timing in patients with chronic obstructive pulmonary disease.

RATIONALE: Little is known about the applicability of respiratory muscle training based on exertional pathophysiological conditions in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the relationship between breathing timing and exertional responses, as well as whether exertional changes in the inspiratory duty cycle (Ti/Ttot) affect pathophysiological conditions, including respiratory muscles. METHODS: Forty-five stable COPD patients (mean age: 71.2 years, severe and very severe COPD: 80%) were evaluated based on exertional cardiopulmonary function and respiratory muscle strength. To compare exertional responses and the balance of inspiratory-to-expiratory muscle strength, the patients were divided into two groups according to whether the Ti/Ttot increased (Ti/Ttot-increased group: resting Ti/Ttot ≤ peak Ti/Ttot, n = 21) or decreased during exercise (Ti/Ttot-decreased group: resting Ti/Ttot > peak Ti/Ttot, n = 24). RESULTS: At peak exercise, the Ti/Ttot was positively correlated with minute ventilation ([Formula: see text] E), and oxygen uptake ([Formula: see text]) in all patients. No significant differences were seen in breathing frequency, tidal volume, or [Formula: see text] E at peak exercise between the two groups. Compared with the Ti/Ttot-increased group, the Ti/Ttot-decreased group had significantly lower mean values of [Formula: see text] and ΔFO2 (the inspired minus expired oxygen concentration) at peak exercise, and significantly higher mean values of the absolute ratio of maximal inspiratory pressure/maximal expiratory pressure. CONCLUSIONS: The exertional change of breathing timing affected exercise tolerance and the balance of inspiratory-to-expiratory muscle strength; this finding might be helpful in making the contradictory choice of managing COPD patients with inspiratory or expiratory muscle training.

The association between erythromycin monotherapy for Mycobacterium avium complex lung disease and cross-resistance to clarithromycin: A retrospective case-series study.

Long-term, low-dose erythromycin monotherapy, based on the anti-inflammatory effects of macrolides, has been reported to have the potential to suppress the exacerbation of Mycobacterium avium complex (MAC) lung disease with less toxicity. It remains unclear whether erythromycin monotherapy induces cross-resistance to clarithromycin, a key drug for MAC. To clarify this point, we conducted a retrospective, single-center, case-series study on patients with MAC lung disease who underwent erythromycin monotherapy for at least 6 months. Drug susceptibility tests, before and after erythromycin treatment initiation, were analyzed. Thirty-three patients were included in our study. All 33 patients showed susceptibility to clarithromycin for MAC both before and after erythromycin monotherapy. There was no significant difference in clarithromycin minimum inhibitory concentrations between before and after erythromycin treatment (median difference = 0 µg/ml; P = .313, Wilcoxon's signed-rank test). We conclude that erythromycin monotherapy for MAC lung disease may not induce cross-resistance to clarithromycin.

Pulmonary rehabilitation for COPD improves exercise time rather than exercise tolerance: effects and mechanisms.

BACKGROUND: COPD patients undergoing pulmonary rehabilitation (PR) show various responses. The purpose of this study was to investigate the possible mechanisms and predictors of the response to PR in COPD patients. METHODS: Thirty-six stable COPD patients underwent PR including a 4-week high-intensity exercise training program, and they were evaluated by cardiopulmonary exercise testing. All patients (mean age 69 years, severe and very severe COPD 94%) were classified into four groups by whether the exercise time (Tex) or the peak oxygen uptake [Formula: see text] increased after PR: two factors increased (both the Tex and the peak [Formula: see text] increased); two factors decreased; time only increased (the Tex increased, but the peak [Formula: see text] economized); and [Formula: see text] only increased (the Tex decreased, but the peak [Formula: see text] increased). Within all patients, the relationships between baseline variables and the post-to-pre-change ratio of the time-slope, Tex/(peak minus resting [Formula: see text]), were investigated. RESULTS: Compared with the two factors increased group (n=11), in the time only increased group (n=18), the mean differences from pre-PR at peak exercise in 1) minute ventilation [Formula: see text] (P=0.004), [Formula: see text] (P<0.0001), and carbon dioxide output [Formula: see text] (P<0.0001) were lower, 2) [Formula: see text]/ [Formula: see text] (P=0.034) and [Formula: see text]/ [Formula: see text] (P=0.006) were higher, and 3) the dead space/tidal volume ratio (VD/VT) and the dyspnea level were similar. After PR, there was no significant difference in the ratio of the observed peak heart rate (HR) to the predicted peak HR (220 - age [years]) between the two groups. A significant negative correlation with the baseline time-slope (r=-0.496, P=0.002) and a positive correlation with the baseline body mass index (BMI) (r=0.496, P=0.002) were obtained. CONCLUSIONS: PR in COPD patients improves Tex rather than exercise tolerance, economizing oxygen requirements, resulting in reduced ventilatory requirements without cardiac loads followed by reduced exertional dyspnea. In addition, the time-slope and BMI could be used to predict PR responses beforehand.

Levels of Antibody against Glycopeptidolipid Core as a Marker for Monitoring Treatment Response in Mycobacterium avium Complex Pulmonary Disease: a Prospective Cohort Study.

The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) is sometimes complicated and time-consuming. A serodiagnostic kit that measures the serum levels of IgA antibodies against the glycopeptidolipid (GPL) core is commercially available and has good diagnostic accuracy for MAC-PD. However, the significance of measurement of GPL core IgA antibody levels in monitoring for chemotherapy response in patients with MAC-PD was not well investigated. Thirty-four treatment naive MAC-PD patients who were started on multidrug chemotherapy were enrolled. Their antibody levels were prospectively measured at regular intervals. The relationships between their antibody levels and the therapeutic outcomes were examined. The patients were classified into three groups (conversion, recurrence, and nonconversion) based on the bacteriological outcomes after chemotherapy. There were no significant differences in the antibody levels before treatment between the culture conversion (n = 19), recurrence (n = 7), and nonconversion (n = 8) groups (P = 0.9881). The levels decreased significantly after the chemotherapy (P < 0.0001). Recurrence and/or worsening of chest radiography findings were observed in cases whose antibody levels subsequently increased after cessation of the chemotherapy. No significant difference in the percent decrease in antibody levels by the chemotherapy was observed between the culture conversion and recurrence groups (P = 0.9338). The initial antibody levels are not a predictor of therapeutic outcomes, and also the percent decrease in antibody levels is not a sufficient indicator of the cessation of chemotherapy. However, serial measurements of antibody levels may allow objective monitoring of disease activity in individual MAC-PD patients.