HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.

The effects of arousal accompanying an apneic event on blood pressure and sympathetic nerve activity in severe obstructive sleep apnea.

PURPOSE: Arousal plays an important protective role against life-threatening events by terminating the apneic events. However, arousal might also be considered as a contributor to obstructive sleep apnea (OSA) pathogenesis since ventilatory overshoot due to arousal leads to irregular breathing. Patients with OSA who have greater upper airway compensation, expressed by relatively high proportion of apneic events without arousal, could have less adverse events or consequences. Thus, our hypothesis was that the proportion of apneic events with or without arousal affects daytime systemic blood pressure and nocturnal sympathetic activity. METHODS: Subjects were consecutive 97 patients who had diagnostic polysomnography (PSG) and showed severe OSA (apnea-hypopnea index ≥ 30). The proportion of apnea-hypopneas with arousal among all apnea-hypopneas was calculated in each patient. Then, the association among the proportion of arousal accompanying apnea-hypopneas and a diagnosis of hypertension or heart rate variability during the PSG were investigated. RESULTS: The proportion of apnea-hypopneas with arousal among all apnea-hypopneas was higher in hypertensive patients (n = 47) than that in normotensive patients (n = 50) (mean ± standard deviation; 80.0 ± 12.8% vs. 73.7 ± 13.0%, p < 0.01). However, heart rate variability was not associated with the proportion of apnea-hypopneas with arousal. CONCLUSIONS: Apnea-hypopneas terminated by arousal are more often present in those with current systemic hypertension but independent of sympathetic nerve activity, compared with those whose apnea-hypopnea events do not have as many arousals. One could target an elevation in arousal threshold as a pathway for reducing daytime blood pressure.

Variability of breathing during wakefulness while using CPAP predicts adherence.

BACKGROUND AND OBJECTIVE: The standard therapy for obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP) therapy. However, long-term adherence remains at ~50% despite improvements in behavioural and educational interventions. Based on prior work, we explored whether regularity of breathing during wakefulness might be a physiologic predictor of CPAP adherence. METHODS: Of the 117 consecutive patients who were diagnosed with OSA and prescribed CPAP, 79 CPAP naïve patients were enrolled in this prospective study. During CPAP initiation, respiratory signals were collected using respiratory inductance plethysmography while wearing CPAP during wakefulness in a seated position. Breathing regularity was assessed by the coefficient of variation (CV) for breath-by-breath estimated tidal volume (VT ) and total duration of respiratory cycle (Ttot). In a derivation group (n = 36), we determined the cut-off CV value which predicted poor CPAP adherence at the first month of therapy, and verified the validity of this predetermined cut-off value in the remaining participants (validation group; n = 43). RESULTS: In the derivation group, the CV for estimated VT was significantly higher in patients with poor adherence than with good adherence (median (interquartile range): 44.2 (33.4-57.4) vs 26.0 (20.4-33.2), P < 0.001). The CV cut-off value for estimated VT for poor CPAP adherence was 34.0, according to a receiver-operating characteristic (ROC) curve. In the validation group, the CV value for estimated VT >34.0 confirmed to be predicting poor CPAP adherence (sensitivity, 0.78; specificity, 0.83). CONCLUSION: At the initiation of therapy, breathing regularity during wakefulness while wearing CPAP is an objective predictor of short-term CPAP adherence.

The effects of heated humidification to nasopharynx on nasal resistance and breathing pattern.

BACKGROUND: Mouth breathing could induce not only dry throat and eventually upper respiratory tract infection, but also snoring and obstructive sleep apnea, while nasal breathing is protective against those problems. Thus, one may want to explore an approach to modify habitual mouth breathing as preferable to nasal breathing. The aim of this study was to investigate the physiological effects of our newly developed mask on facilitation of nasal breathing. METHODS: Thirty seven healthy male volunteers were enrolled in a double blind, randomized, placebo-controlled crossover trial. Participants wore a newly developed heated humidification mask or non-heated-humidification mask (placebo) for 10-min each. Subjective feelings including dry nose, dry throat, nasal obstruction, ease to breathe, relaxation, calmness, and good feeling were asked before and after wearing each mask. In addition, the effects of masks on nasal resistance, breathing pattern, and heart rate variability were assessed. RESULTS: Compared with the placebo mask, the heated humidification mask improved all components of subjective feelings except for ease to breathe; moreover, decreased nasal resistance and respiratory frequency accompanied a simultaneous increase in a surrogate maker for tidal volume. However, use of the heated humidification mask did not affect heart rate variability. CONCLUSION: Adding heated humidification to the nasopharynx could modulate breathing patterns with improvement of subjective experience and objective nasal resistance.

Prevalence of chronic obstructive pulmonary disease in independent community-dwelling older adults: The Fujiwara-kyo study.

AIM: As the Japanese population ages, the number of older patients with chronic obstructive pulmonary disease (COPD) is expected to increase, but the prevalence of COPD in patients aged ≥80 years remains unclear. The purpose of the present study was to determine the prevalence of COPD in independent community-dwelling older adults aged ≥80 years. METHODS: We investigated the prevalence of COPD in 2862 independent community-dwelling older adults (1504 men, 1358 women, mean age 77.7 ± 7.0 years) who underwent spirometry in the Fujiwara-kyo study, a study of successful aging in older adults. Those participants with airflow limitation (forced expiratory volume in 1 s/forced vital capacity <0.7) who indicated on a self-administered questionnaire that they had a history of smoking and did not have bronchial asthma were considered to have COPD. RESULTS: The prevalence of COPD was 16.9% among all participants and 37.4% among smokers. The prevalence among individuals aged ≥80 years (19.7%) was significantly higher than that among those aged <80 years (16.0%; P < 0.05). When forced expiratory volume in 1 s/forced vital capacity lower limit of normal was used as the criterion for airflow limitation, the prevalence fell to 11.0%. Patients with mild-to-moderate airflow limitation (stage I/stage II) accounted for the great majority (91.2%) of COPD patients aged ≥80 years. CONCLUSIONS: A high prevalence of mild-to-moderate COPD was observed even in the independent community-dwelling older adults aged ≥80 years. However, the benefits of the spirometric screening and treatment for these patients needs to be determined. Geriatr Gerontol Int 2017; 17: 2421-2426.