A case of endobronchial mucosa-associated lymphoid tissue (MALT) lymphoma successfully treated with radiotherapy and a review of the literature.

A 60-year-old man was noted to have an elevated lesion in the right mainstem bronchus on chest computed tomography (CT) during his annual medical checkup 3 years previously. The lesion had gradually increased in size. FDG-PET showed no accumulation. Bronchoscopy revealed 5 nodular smooth surface protrusions on the ventral surface of the right mainstem bronchus, with the largest lesion that measured 5 mm in diameter. Biopsy showed diffuse infiltration of small lymphocytes, positive for CD20 and subsequently diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. The lesions disappeared on chest CT after radiotherapy, and no recurrence has been observed after 5 years. We reviewed 48 cases of endobronchial MALT lymphoma in the literature and provided a comprehensive review of the literature to date including our case.

Variation of respiratory and pulse events in multiple system atrophy.

INTRODUCTION: A study is eagerly awaited that will reveal the unknown mechanisms of multiple system atrophy (MSA), in which the risk of sudden death is the greatest during sleep. The blunted pulse response to nocturnal respiratory events suggests an abnormal cardiac response to a sleep-related breathing disorder. Patients with MSA have a lower pulse event index (PEI), despite a greater hypoxic burden and a similar frequency of respiratory events. However, the evidence is speculative and not directly proven, and many limitations require further study. METHODS: We conducted a retrospective analysis of 26 patients with MSA who had undergone overnight oximetry between April 2016 and December 2022. RESULTS: The median 4% oxyhemoglobin desaturation index (ODI) was 11.6/h, the 6-bpm PEI was 8.9/h, and the PEI/ODI ratio was as low as 0.91. There were three patients with suspected sudden death; all had low PEI/ODI ratios. The PEI/ODI ratio was followed over time in seven patients, all of whom had a decrease in the ratio. However, the PEI was higher than the ODI in 12/26 (46%) of the patients. CONCLUSION: A low PEI/ODI ratio, reflecting a blunted pulse response to nocturnal respiratory events in patients with MSA, may indicate a worse prognosis. This finding and the significance of the longitudinal decrease in the PEI/ODI ratio will require a prospective study.

Continuous positive airway pressure treatment reduces renal tubular damage in patients with obstructive sleep apnea: A retrospective single-center cohort study.

BACKGROUND: Chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of obstructive sleep apnea (OSA) comorbidities. The prevalence of chronic kidney disease is higher in patients with OSA than the general population, and renal function decline is well correlated with renal tubular injury. However, little is known about the impact of OSA-induced chronic IH on the renal tubules. METHODS: We conducted a retrospective survey of clinical records performing multiple regression analysis and cluster analysis with particular attention to the 3% oxygen desaturation index (ODI) and urinary N-acetyl-ß-d-glucosaminidase (NAG). RESULTS: In patients with suspicion of OSA, urinary NAG creatinine ratio (UNCR) was elevated as their 3% ODI increased (n = 197, p < 0.001), and the elevated UNCR decreased following CPAP treatment in patients with OSA (n = 46, p = 0.014). Multiple regression analysis showed that 3% ODI was associated with UNCR. Cluster analysis identified three clusters of patients with OSA, including two younger age clusters, one of which was characterized by high BMI, high 3% ODI, and high prevalence of major comorbidities. In a comparative analysis of younger age cases (age ≤ 55, n = 82), the UNCR level was higher in patients with severe 3% ODI (3% ODI > 40 events/h, n = 24) (p = 0.014). CONCLUSIONS: Our results indicate that even at younger ages, OSA patients with severe chronic IH and major comorbidities are susceptible to renal tubular damage. Early treatment with CPAP may attenuate renal tubular injury and progression toward end-stage renal disease.

The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome.

Nasal breathing disorders are associated with obstructive sleep apnea (OSA) syndrome and influence the availability of continuous positive airway pressure (CPAP) therapy. However, information is scarce about the impact of nasal resistance assessed by rhinomanometry on CPAP therapy. This study aimed to examine the relationship between CPAP adherence and nasal resistance evaluated by rhinomanometry, and to identify clinical findings that can affect adherence to CPAP therapy for patients with OSA. This study included 260 patients (199 men, 61 women; age 58 [interquartile ranges (IQR) 50-66] years) with a new diagnosis of OSA who underwent rhinomanometry (before, and 1 and 3 months after CPAP introduction) between January 2011 and December 2018. CPAP use was recorded, and the good and poor CPAP adherence groups at the time of patient registration were compared. Furthermore, those with improved and unimproved pre-CPAP high rhinomanometry values were also compared. Their apnea-hypopnea index (AHI) by polysomnography at diagnosis was 45.6 (IQR 33.7-61.6)/hour, but the residual respiratory event (estimated AHI) at enrollment was 2.5 (IQR 1.4-3.9)/hour and the usage time was 318 (IQR 226-397) minutes, indicating that CPAP was effective and adherence was good. CPAP adherence was negatively correlated with nasal resistance (r = -0.188, p = 0.002). The participants were divided into good (n = 153) and poor (n = 107) CPAP adherence groups. In the poor adherence group, rhinomanometry values before CPAP introduction were worse (inspiration, p = 0.003; expiration, p = 0.006). There was no significant difference in patient background when comparing those with improved (n = 16) and unimproved (n = 12) pre-CPAP high rhinomanometry values. However, CPAP usage time was significantly longer in the improved group 1 month (p = 0.002) and 3 months (p = 0.026) after CPAP introduction. The results suggest that nasal resistance evaluated by rhinomanometry is a useful predictor of CPAP adherence, and that improved rhinomanometry values may contribute to extending the duration of CPAP use.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population.

INTRODUCTION: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. RESULTS: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. DISCUSSION/CONCLUSION: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

A 48-Year-Old Man With Multiple Pulmonary Nodular Opacities and Elevated KL-6 Level.

CASE PRESENTATION: A 48-year-old man was referred for evaluation of an abnormal chest shadow noted on a routine chest radiograph during physical examination. He was asymptomatic and had no significant medical history and occupational exposure. The patient lived in Tokyo and had no significant travel history. He had smoked approximately 20 cigarettes daily for 20 years. He had no illicit drug use and no animal-rearing history.

Hypobaric hypoxia is not a direct dyspnogenic factor in healthy individuals at rest.

Dyspnea consists of various uncomfortable respiratory sensations. It is believed that hypoxia causes dyspnea, but whether hypoxia is a direct dyspnogenic factor remains uncertain. We investigated whether hypoxia has a direct dyspnogenic effect. We evaluated changes in vital signs, arterial blood gases, SaO2, CaO2, Borg scale, and Mini-Mental State Examination in seven mountain climbers by using a hypobaric hypoxic chamber in which the barometric pressure was lowered to the simulated altitude of 4500 m. PaO2 and CaO2 both decreased significantly as the simulated altitude increased. On the other hand, Borg scale score which reflects dyspnea showed no significant difference. At the simulated altitude of 4500 m, Borg scale score was 1.5 ± 1.2 (mean ± SD), despite the presence of absolute hypoxia (PaO2, 46.8 ± 8.3T; CaO2, 16.4 ± 0.6 mL/dL). These results suggest that hypoxia is not a direct dyspnogenic factor in healthy individuals capable of breathing without restriction at rest.

Significant relationship between platelet activation and apnea-hypopnea index in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for arterial thrombosis, which is associated with high cardiovascular morbidity and mortality. To investigate the possible involvement of activated platelets, we evaluated the relationship between severity of OSAS and appearance of platelet aggregates (a marker of activated platelets) in 35 OSAS patients. Platelet aggregates were quantitatively determined by means of flow cytometry. There was a significant correlation between platelet aggregates and apnea-hypopnea index in the severe (AHI≥30 events/hour) group (r=0.756, p<0.001), but not in the mild-moderate (5≤AHI<30 events/hour) group (r=-0.032, p=0.905). The results indicate that the appearance of platelet aggregates increases with an increase in the severity of OSAS.

Polycythemia and changes in erythropoietin concentration in rats exposed to intermittent hypoxia.

It is not clear whether blood hemoglobin concentration ([Hb]) increases with an increase in the exposure period of intermittent hypoxia (IHx) and reaches a constant level. Furthermore, it is not known whether plasma erythropoietin concentration ([EPO]) also increases with an increase in the exposure period. Using a rat model, first, we evaluated changes in [EPO] every hour after single exposure of 10% O(2) for 120 min in order to determine a peak level of [EPO]. Second, we evaluated the effect of IHx of 10% O(2), 120 min/day for 0 (control), 1, 2, 3, 4, 6 and 8 weeks on [Hb], arterial blood pressure (BP), heart rate (HR), arterial blood gases (ABGs) and [EPO]. [EPO] increased after cessation of the single hypoxic exposure, reached a peak at 1 h, and decreased gradually to the control levels within 18 h. IHx of 10% O(2), 120 min/day, produced a time-dependent increase in [Hb], and [Hb] reached a constant level after the exposure for 6 weeks. BP increased after the exposure for 4 weeks and remained elevated. There was no significant difference in HR and ABGs. [EPO] increased significantly and remained elevated at the same level for 1-3 weeks, however, the peak level of [EPO] declined markedly after [Hb] reached a constant level.

A case of HAPE on K2 and literature review.

HAPE (High Altitude Pulmonary Edema) is a serious and fatal disease in mountains. Early diagnosis and immediate descent are important for successful treatment. One of the authors (GS), who was healthy and a well trained climber, participated in the expedition to K2 (8611 m) in 2006 and developed HAPE. Under the severe environmental condition, it was difficult to evaluate his condition in its early stage. The earliest symptoms were nonspecific for HAPE as reported in many papers. Neither had he suffered from HAPE on the previous expeditions. These facts probably delayed the diagnosis in spite of its typical onset. This is a rare case report by a medical doctor who suffered from HAPE. The present case may remind the climbers of the difficulties in diagnosing HAPE on a mountain.

Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in healthy subjects and patients with COPD.

[Background] In patients with chronic obstructive pulmonary disease (COPD), early lactic acidosis during exercise should be considered as playing a role in the limitation of exercise tolerance. It was hypothesized that the relationship between blood lactate concentrations (LA) and tissue oxygenation index (TOI) is available for the prediction of aerobic capacity of skeletal muscle. [Methods] Changes of LA and TOI in the vastus lateralis muscle were measured during incremental cycling exercise in 12 healthy subjects and 4 patients with COPD. The relationship between TOI and LA was examined in 12 healthy subjects and 4 COPD patients, and changes in the relationship were examined at an interval of several years (3.3 +/- 1.0). [Results] (1) From the pattern LA as related to TOI, the healthy subjects were classified into the three groups. Group A (n = 3); LA increased slowly with a decrease in TOI. Group B (n = 3); LA increased steeply after the half point of maximal exercise. Group C (n = 6); LA increased steeply before the half point of maximal exercise. (2) In 3 patients with COPD, the relationship between TOI and LA shifted rightward at the second examination. [Conclusion] The steep increase in LA from the approximate resting value of TOI during exercise suggests that the aerobic capacity of working skeletal muscle decreased.

[Effects of chronic repetitive hypercapnic hypoxia on systemic and pulmonary hemodynamics in a rat model].

We determined the effects of chronic repetitive hypoxia and hypercapnic hypoxia on systemic and pulmonary hemodynamics using an animal model simulating sleep apnea syndrome (SAS). Fifty-six rats were divided into the hypoxia (Pao2 44-46Torr) and the hypercapnic hypoxia (Pao2 44-46Torr, Paco2 48-49Torr) group. The hypoxic gas or the hypercapnic hypoxic gas was flushed into the chamber for 1 min, then air was flushed allowing return of gas fractions to ambient levels for 3 min. Each cycle was repeated 6h/day for 5 weeks. In the hypoxia group, there was no significant difference in baseline blood pressure (BP) and heart rate (HR) between controls and the exposure group. Only HR increased transiently during hypoxia in both controls and the exposure group. RV/(LV + S) did not change after 5 weeks of exposure. In the hypercapnic hypoxia group, there was no significant difference in baseline BP and HR between controls and the exposure group. However, acute BP elevation and transient bradycardia were induced during hypercapnic hypoxia, and the magnitude of the changes increased with an increase in the exposure period. RV/(LV + S) increased after 5 weeks of exposure. Phentolamine attenuated acute BP elevation and atropine abolished bradycardia, suggesting an increased sympathetic and parasympathetic tone. The results suggest that hypercapnia associated with hypoxia plays an important role in developing cardiovascular changes in SAS.