The Contribution of Genetic Variants of the Peroxisome Proliferator-Activated Receptor-Alpha Gene to High-Altitude Hypoxia Adaptation in Sherpa Highlanders.

Kinota, Fumiya, Yunden Droma, Nobumitsu Kobayashi, Toshimichi Horiuchi, Yoshiaki Kitaguchi, Masanori Yasuo, Masao Ota, and Masayuki Hanaoka. The contribution of genetic variants of the gene encoding peroxisome proliferator-activated receptor-alpha gene (PPARA) to high-altitude hypoxia adaptation in Sherpa highlanders. High Alt Med Biol. 24:186-192, 2023.-Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia. Sherpa people are well known to possess the traits determined by genetic background for high-altitude adaptation. The metabolic adaptation mechanism is one of the biological ways for Sherpa highlanders in protecting them from hypoxia stress at high altitude. Studies have suggested that the gene encoding PPARA is associated with metabolic adaptation in the Himalayan population of Tibetans. This study attempts to investigate the genetic variants of the PPARA in Sherpa highlanders and the association with high-altitude hypoxia adaptation. Seven single-nucleotide polymorphisms (SNPs; rs135547, rs5769178, rs881740, rs4253712, rs5766741, and rs5767700 in introns and rs1800234 in exon 6) in the PPARA were genotyped in 105 Sherpa highlanders who lived in the Khumbu region (3440 m above sea level) and 111 non-Sherpa lowlanders who resided in Kathmandu (1300 m) in Nepal. By means of analyses of genetic distances, genotype distributions, allele frequencies, linkage disequilibrium, and haplotype constructions of the seven SNPs in the Sherpa highlanders versus the non-Sherpa lowlanders, it was revealed that the frequencies of minor alleles of rs4253712, rs5766741, rs5767700, and rs1800234 SNPs, as well as the frequency of haplotype constructed by the minor alleles of rs5766741-rs5767700-rs1800234, were significantly overrepresented in the Sherpa highlanders in comparison with the non-Sherpa lowlanders. The results strongly suggest that the genetic variants of the PPARA are likely to contribute to the high-altitude adaptation in Sherpa highlanders.

Probe-based optical fiberscopy for the direct observation of peripheral pulmonary lesions.

BACKGROUND: Peripheral pulmonary lesions are rarely observed directly before transbronchial biopsy. This study aimed to characterize the differences between malignant and benign peripheral pulmonary lesions according to the findings of direct observation using probe-based optical fiberscopy. METHODS: Thirty patients who underwent probe-based optical fiberscopy in combination with bronchoscopy using endobronchial ultrasonography with a guide sheath for the evaluation of peripheral pulmonary lesions were prospectively included in this study. The patients were divided into the malignant and benign groups according to their final diagnosis. The findings of probe-based optical fiberscopy in the two groups were compared. RESULTS: The numbers of patients who were diagnosed using histological or bacteriological analyses via bronchoscopic sampling in the malignant and benign groups were 20/23 (87.0%) and 2/7 (28.6%), respectively. On probe-based optical fiberscopy, angiogenesis and vascular engorgement were observed only in the malignant group. The disappearance of subepithelial microvessel transparency and presence of bronchiolar stenosis were observed more frequently in the malignant group (78.3% and 60.9%) than in the benign group (28.6% and 28.6%), whereas increased mucus secretion was observed more frequently in the benign group (71.4%) than in the malignant group (8.7%). CONCLUSIONS: These results suggest that the findings of direct observation using probe-based optical fiberscopy are useful for differentiating malignant from benign peripheral pulmonary lesions. TRIAL REGISTRY: UMIN-CTR; UMIN000018796; URL: https://www.umin.ac.jp/ctr/index.htm.

Usefulness of the forced oscillation technique in assessing the therapeutic result of tracheobronchial central airway obstruction.

BACKGROUND: Pulmonary function tests (PFTs) comprise the traditional method for detecting central airway obstruction (CAO) and evaluating therapeutic effects, but are effort-dependent. By contrast, the forced oscillation technique (FOT) is performed during tidal breathing in an effort-independent mode and is universally used to assess respiratory function in patients with chronic obstructive pulmonary disease (COPD) and asthma. We used the FOT to measure airway resistance and reactance in patients with CAO before and after interventional bronchoscopy and compared the results to data obtained using PFTs. METHODS: Twelve patients with CAO were recruited from December 2013 to July 2016. The FOT, PFTs, chest computed tomography (CT), COPD Assessment Test (CAT), and the modified Medical Research Council (mMRC) dyspnea scale were employed before and after interventional bronchoscopy. The minimum airway cross-sectional area (MACSA) was calculated using a CT image calculator. RESULTS: Of the 12 patients, 6 had tracheal obstruction and 6 had bronchial obstruction. All FOT measurements, except ΔX5, were significantly improved after interventional bronchoscopy in all cases. The significance of the improvement was greater with the FOT than PFTs. The MACSA, CAT, and mMRC dyspnea scale scores also significantly improved in all cases. Furthermore, only alteration of resistance at 20 Hz (R20) significantly correlated with the alteration of the MACSA after intervention. No significant correlations were found for PFTs. CONCLUSIONS: The FOT is suitable and convenient for assessing therapeutic results in patients with tracheobronchial CAO. The alteration of R20 is useful for estimating the airway dilation of CAO after interventional bronchoscopy.