A Preliminary Genome-Wide Association Study of Acute Mountain Sickness Susceptibility in a Group of Nepalese Pilgrims Ascending to 4380 m.

There is significant interindividual variation in acute mountain sickness (AMS) susceptibility in humans. To identify genes related to AMS susceptibility, we used a genome-wide association study (GWAS) to simultaneously test associations between genetic variants dispersed throughout the genome and the presence and severity of AMS. DNA samples were collected from subjects who ascended rapidly to Gosainkunda, Nepal (4380 m), as part of the 2005, 2010, and 2012 Janai Purnima festivals. The Lake Louise Score was used to measure AMS severity. The primary analysis was based on 99 male subjects (43 with AMS; 56 without AMS). Genotyping for the GWAS was performed using Infinium Human Core Exome Bead Chips (542,556 single-nucleotide polymorphisms were assayed), and validation genotyping was performed with pyrosequencing in two additional cohorts (n = 101 for each). In total, 270,389 single nucleotide polymorphisms (SNPs) passed quality control, and 4 SNPs (one intronic, three nonsynonymous) in the FAM149A gene were associated with AMS severity after correcting for multiple hypothesis testing (p = 1.8E-7); however, in the validation cohorts, FAM149A was not associated with the presence or severity of AMS. No other genes were associated with AMS susceptibility at the genome-wide level. Due to the large influence of environmental factors (i.e., ascent rate and altitude attained) and the difficulties associated with the AMS phenotype (i.e., low repeatability, nonspecific symptoms, potentially independent ailments), we suggest that future studies addressing the variation in the acute human hypoxia response should focus on objective responses to acute hypoxia instead of AMS.

Acute mountain sickness, chemosensitivity, and cardiorespiratory responses in humans exposed to hypobaric and normobaric hypoxia.

We examined the control of breathing, cardiorespiratory effects, and the incidence of acute mountain sickness (AMS) in humans exposed to hypobaric hypoxia (HH) and normobaric hypoxia (NH), and under two control conditions [hypobaric normoxia (HN) and normobaric normoxia (NN)]. Exposures were 6 h in duration, and separated by 2 wk between hypoxic exposures and 1 wk between normoxic exposures. Before and after exposures, subjects (n = 11) underwent hyperoxic and hypoxic Duffin CO2 rebreathing tests and a hypoxic ventilatory response test (HVR). Inside the environmental chamber, minute ventilation (V(E)), tidal volume (V(T)), frequency of breathing (fB), blood oxygenation, heart rate, and blood pressure were measured at 5 and 30 min and hourly until exit. Symptoms of AMS were evaluated using the Lake Louise score (LLS). Both the hyperoxic and hypoxic CO2 thresholds were lower after HH and NH, whereas CO2 sensitivity was increased after HH and NH in the hypoxic test and after NH in the hyperoxic test. Values for HVR were similar across the four exposures. No major differences were observed for Ve or any other cardiorespiratory variables between NH and HH. The LLS was greater in AMS-susceptible than in AMS-resistant subjects; however, LLS was alike between HH and NH. In AMS-susceptible subjects, fB correlated positively and Vt negatively with the LLS. We conclude that 6 h of hypoxic exposure is sufficient to lower the peripheral and central CO2 threshold but does not induce differences in cardiorespiratory variables or AMS incidence between HH and NH.

A prospective epidemiological study of acute mountain sickness in Nepalese pilgrims ascending to high altitude (4380 m).

BACKGROUND: Each year, thousands of pilgrims travel to the Janai Purnima festival in Gosainkunda, Nepal (4380 m), ascending rapidly and often without the aid of pharmaceutical prophylaxis. METHODS: During the 2012 Janai Purnima festival, 538 subjects were recruited in Dhunche (1950 m) before ascending to Gosainkunda. Through interviews, subjects provided demographic information, ratings of AMS symptoms (Lake Louise Scores; LLS), ascent profiles, and strategies for prophylaxis. RESULTS: In the 491 subjects (91% follow-up rate) who were assessed upon arrival at Gosainkunda, the incidence of AMS was 34.0%. AMS was more common in females than in males (RR = 1.57; 95% CI = 1.23, 2.00), and the AMS incidence was greater in subjects >35 years compared to subjects ≤35 years (RR = 1.63; 95% CI = 1.36, 1.95). There was a greater incidence of AMS in subjects who chose to use garlic as a prophylactic compared to those who did not (RR = 1.69; 95% CI = 1.26, 2.28). Although the LLS of brothers had a moderate correlation (intraclass correlation = 0.40, p = 0.023), sibling AMS status was a weak predictor of AMS. CONCLUSIONS: The incidence of AMS upon reaching 4380 m was 34% in a large population of Nepalese pilgrims. Sex, age, and ascent rate were significant factors in the development of AMS, and traditional Nepalese remedies were ineffective in the prevention of AMS.

Femoroacetabular impingement syndrome: an underrecognized cause of hip pain and premature osteoarthritis?

Acetabular dysplasia is well recognized as a potential predisposing factor to the development of hip osteoarthritis (OA). In the orthopedic literature, other dysmorphic and orientation abnormalities of the femoral head, femoral head-neck junction, and the acetabulum have been reported, with increasing frequency in recent years, under the term femoroacetabular impingement syndrome (FAI). The studies have shown a clear association of these structural anomalies with patients' symptoms and signs, radiographic and pathologic abnormalities, and the development of degenerative hip arthritis. FAI is now believed to be a very important predisposing factor for the development of degenerative hip arthritis, particularly in younger adults. Although the results of longterm studies are awaited, the hope is that early surgical intervention in patients with FAI will change the course or prevent the development of hip OA. It is well documented that early recognition of potential FAI surgical candidates, before OA is advanced, determines the postsurgical outcome. FAI has not been reported in the rheumatology literature, but since patients with FAI likely often initially present to rheumatology clinics for assessment of hip pain, it is important for rheumatologists to be aware of this condition and refer to orthopedics when appropriate. The objective of this review is to provide an outline of the basic concepts of FAI, including clinical presentation and radiographic findings, so that rheumatologists become more familiar with this important emerging entity.