In-hospital pulmonary rehabilitation after completion of primary respiratory disease treatment improves physical activity and ADL performance: A prospective intervention study.

INTRODUCTION: Pulmonary rehabilitation improves the physical condition of patients with chronic respiratory disease; however, there are patients who cannot leave the hospital because of their low activities of daily living (ADLs), despite the completion of primary respiratory disease treatment and rehabilitation during treatment. Therefore, this study demonstrated that those patients recovered their ADLs through in-hospital pulmonary rehabilitation after treatment completion. METHODS: We prospectively studied 24 hospitalized patients who had some remaining symptoms and showed low ADL scores of 9 points or less on the short physical performance battery after undergoing treatment for respiratory disease in Fukujuji Hospital from October 2018 to October 2019, excluding 2 patients who had re-exacerbation and 1 patient who could not be examined using the incremental shuttle walk test (ISWT). After completion of the primary respiratory disease treatment, patients moved to the regional comprehensive care ward, and they received pulmonary rehabilitation for 2 weeks. In the ward, patients who could not yet leave the hospital could undergo pulmonary rehabilitation for up to 60 days. Data were evaluated three times: upon treatment completion (baseline), postrehabilitation, and 3 months after baseline. The main outcome was an improvement in the incremental shuttle walk test (ISWT) postrehabilitation. RESULTS: The median age of the patients was 80 (interquartile range (IQR): 74.8-84.5), and 14 patients (58.3%) were male. The ISWT distance significantly increased postrehabilitation (median [IQR]: 60 m [18-133] vs 120 m [68-203], P < .001). The Barthel Index (BI) (P < .001), the modified Medical Research Council (P < .001), and other scale scores were also improved. Among patients with acute respiratory diseases such as pneumonia, chronic obstructive pulmonary disease, and interstitial pneumonia, ISWT and other data showed improvement at the postrehabilitation timepoint. Ten patients who could perform examinations at 3 months after baseline were evaluated 3 months after taking baseline data prior to starting rehabilitation. The ISWT showed significant improvement 3 months after baseline compared to baseline (P = .024), and the ISWT distance was maintained after rehabilitation. DISCUSSION AND CONCLUSIONS: Physical activity, symptoms, mental health, and ADL status in patients who had not recovered after primary treatment completion for respiratory diseases could improve through in-hospital pulmonary rehabilitation.

Minimum Inhibitory Concentrations before and after Antibacterial Treatment in Patients with Mycobacterium abscessus Pulmonary Disease.

The clinical importance of Mycobacterium abscessus (MABS) pulmonary disease has been increasing. However, there is still a lack of information about MIC distribution patterns and changes in clinical practice settings. The MIC results of rapidly growing mycobacteria isolated from 92 patients with nontuberculous mycobacterial pulmonary disease diagnosed from May 2019 to March 2021 were retrospectively analyzed. Most of the patients (86 patients; 93.5%) were infected with MABS; 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma). Significant differences in susceptibility to clarithromycin (15.2% versus 80.0%, P < 0.001) and azithromycin (8.7% versus 62.5%, P < 0.001) were observed between Mab and Mma. Most isolates were susceptible to amikacin (80; 93.0%), and over half were susceptible to linezolid (48; 55.8%). Only one-quarter of isolates (22, 25.6%) were susceptible to imipenem, while more than half (56; 65.1%) had intermediate susceptibility. Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, which were significantly higher than isolates for moxifloxacin (5; 5.8%), especially in Mab. Sixty-five (75.6%) isolates had MICs of less than 0.5 µg/mL to clofazimine. Two patients showed obvious MIC result changes: from susceptible to resistant to clarithromycin and from resistant to susceptible to amikacin and imipenem. In conclusion, MABS isolates were relatively susceptible to amikacin and linezolid, and clarithromycin and azithromycin were especially effective against Mma. In addition, sitafloxacin and clofazimine had low MICs and might be effective treatment agents. IMPORTANCE The MICs of isolates from 86 patients with Mycobacterium abscessus (MABS); 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma) were retrospectively analyzed. The main findings are as follows: (i) Mma were significantly more susceptible to clarithromycin and azithromycin than Mab, and both subspecies tended to be more susceptible to clarithromycin than azithromycin. (ii) Most isolates were susceptible to amikacin (93.0%), and over half to linezolid (55.8%). (iii) Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, and 65 (75.6%) had less than 0.5 µg/mL for clofazimine, which seems worth clinical investigating. (iv) Among nine cases analyzed chronological changes, only two patients showed obvious MIC result changes even after the long-term multidrug treatment. The present study revealed MICs of MABS clinical isolates before and after treatment in clinical settings, which could help develop future MABS treatments strategies.

Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease.

BACKGROUND: Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease. METHODS: Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 µg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings. RESULTS: Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found. CONCLUSIONS: Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

The impact of co-existing seasonal allergic rhinitis caused by Japanese Cedar Pollinosis (SAR-JCP) upon asthma control status.

BACKGROUND: Seasonal Allergic Rhinitis Caused by Japanese Cedar Pollinosis (SAR-JCP) is a most common allergic rhinitis, affecting about 40% in Japan, but the influence from SAR-JCP upon asthma is controversial. The purpose of this study is to investigate the effect of coexistence of SAR-JCP upon control status of asthma using SACRA (Self-Assessment of Allergic Rhinitis and Asthma Questionnaire). METHODS: The design was prospective, single-center, observational study. Asthmatic patients were classified into 3 groups, patients without rhinitis, those with perennial rhinitis or those with SAR-JCP from the results of SACRA. The control status of asthma were evaluated by Visual Analog Scale (VAS) in SACRA and Asthma Control Test (ACT) score. They were evaluated twice, from September to January (nonpollen-season) and February to April (pollen-season) and compared. RESULTS: 451 patients were enrolled and 325 cases (72%) were diagnosed as having comorbidity of rhinitis, among which 173 with only perennial rhinitis, while 152 with SAR-JCP. There was no significant difference in asthma control level measured by VAS and ACT score among 3 groups during nonpollen-season. The asthma control level measured by VAS (1.91-2.95) and ACT score (22.7-21.6) got worse during pollen-season among patients with SAR-JCP, even though 84% received treatment for rhinitis. Although it differed according to criteria, asthma control during pollen-season was impaired in 18-38% asthmatic patients with SAR-JCP. CONCLUSION: It is possible to minimize the influence of AR on asthma control by obtaining an accurate diagnosis and providing sufficient treatment for rhinitis.

Japanese Guideline for Adult Asthma 2014.

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting ß2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled ß2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

A unique pattern of bisphenol a effects on nerve growth factor gene expression in embryonic mouse hypothalamic cell line N-44.

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 µmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 µmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 µmol L-1 the NgfmRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.

Gene expression of epigenetic regulatory factors related to primary silencing mechanism is less susceptible to lower doses of bisphenol A in embryonic hypothalamic cells.

DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells, with particular emphasis on the gene expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose-dependent (0.02-200 µM BPA) 3-hr experiment, real-time reverse transcription polymerase chain reaction revealed that gene expression of both Dnmts and Mecp2_e2 was affected at 200 µM and that of Mecp2_e1 was affected at > 20 µM. These results suggest that gene expression of Dnmts and Mecp2 are less susceptible to lower doses of BPA in developing hypothalamic cells. However, as BPA concentration increases, this agent has the potential to alter gene expression of key players that provide stability and flexibility of epigenetic gene regulation, which could disrupt the normal development of hypothalamic functions.

Docosahexaenoic acid exerts anti-inflammatory action on human eosinophils through peroxisome proliferator-activated receptor-independent mechanisms.

BACKGROUND: Despite the fact that previous studies have indicated the significant roles of polyunsaturated fatty acids (PUFAs) in the immune system through peroxisome proliferator-activated receptor alpha (PPARα) and PPARγ, the biological functions and the mechanisms of action in eosinophils are poorly understood. METHODS: We investigated the functional effects of docosahexaenoic acid (DHA, n-3 PUFA) on human peripheral blood eosinophils, using in vitro systems to test the hypothesis that DHA negatively regulates eosinophil mechanisms through PPARα and PPARγ. RESULTS: Eosinophil apoptosis that spontaneously occurs under normal culture conditions was accelerated in the presence of DHA. In addition, eotaxin-directed eosinophil chemotactic responses were inhibited by pretreatment with DHA, disturbing both the velocity and the directionality of the cell movement. Pharmacological manipulations with specific antagonists indicated that the effects of DHA were not mediated through PPARα and PPARγ, despite the presence of these nuclear receptors. DHA also induced Fas receptor expression and caspase-3 activation that appears to be associated with a proapoptotic effect of DHA. Further, DHA rapidly inhibited the expression of eotaxin receptor C-C chemokine receptor 3 and eotaxin-induced calcium influx and phosphorylation of extracellular signal-regulated kinase. Interestingly, these inhibitory effects were not observed with linoleic acid (n-6 PUFA). CONCLUSIONS: The data might explain one of the mechanisms found in previous research showing the favorable effects of n-3 PUFA supplementation on allergic diseases, and provide novel therapeutic strategies to treat eosinophilic disorders.

Blocking antibody is generated in allergic rhinitis patients during specific immunotherapy using standardized Japanese cedar pollen extract.

BACKGROUND: Japanese cedar pollen is by far the most important cause of allergic rhinitis in Japan. In this study, we assessed the induction of blocking antibody during specific immunotherapy (SIT) using a recently standardized allergen extract from Japanese cedar pollen. METHODS: Basophils from nonallergic subjects were passively sensitized with serum samples prepared from pollinosis patients before and after SIT; all patients showed good clinical efficacy. The cells were then stimulated with the standardized allergen, and histamine release was measured. In most experiments, the basophil stimulation buffer contained 1% serum. RESULTS: Pollinosis patients' sera obtained both before and after SIT showed essentially similar sensitizing capacity for basophils. Basophil degranulation in response to a relatively low concentration of pollen extract was effectively suppressed by addition of post-SIT serum samples, indicating the presence of blocking antibody. The blocking antibody was IgG, and its potency varied widely among the donor patients. CONCLUSIONS: The standardized allergen extract from Japanese cedar pollen is useful not only for clinical application in SIT, but also for testing for induction of blocking antibody during SIT.