Lake Louise Questionnaire Score Research Articles

Mitochondrial DNA Variation Correlated With the High Altitude Intolerance in Chinese Young Han Males.

ObjectiveAcute exposure to hypobaric hypoxia can trigger acute mountain sickness (AMS), while the exact mechanism has not been fully revealed. The role of genetic factors in the susceptibility of various high-altitude diseases has also gained much interest. Previous studies have provided evidence for the link between AMS and certain nuclear genes or mitochondrial haplogroup. The correlation between point mutations of mitochondrial DNA (mtDNA) and AMS was further explored in the present study.MethodsA total of 84 young Han males residing at low altitude were taken to an elevation of 4,000 m within 40 h. We collected data of their heart rate, blood pressure, peripheral oxygen saturation (SaO2), and obtained blood samples, at sea level and at high altitude. AMS was diagnosed using the revised version of the Lake Louise Questionnaire Score. Sequencing was utilized to identify the association between mtDNA alleles and the occurrence of AMS. We also assessed the association between the presence of AMS and physiological variables, and provided a preliminary discussion of the association between genotypic and phenotypic variation.ResultsThe percentage of neutrophils [Odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01–1.12, P = 0.034) and SaO2 level (OR: 0.87, 95% CI: 0.79–0.95, P = 0.004) were independently associated with the development of AMS. A4576G was a risk factor for AMS (OR: 6.27, 95% CI: 1.2–32.7). T11613C (OR: 0.10, 95% CI: 0.01–0.83), A8923G (OR: 0.15, 95% CI: 0.03–0.76), and T5543C (OR: 0.19, 95% CI: 0.04–0.95) were protective factors for AMS. The level of SaO2 was significantly lower in the individual with A4576G mutation as compared with the individual without A4576G mutation (68.1 ± 7.9 vs. 75.8 ± 6.1, P = 0.001). The level of serum sodium was significantly higher in the individual with A8923G mutation as compared to the individual without A8923G mutation (144.6 ± 1.9 vs. 143.2 ± 1.9, P = 0.027).ConclusionsThe increase in neutrophils and the disability to preserve oxygen saturation may be associated with the high altitude intolerance in young Chinese Han males. A4576G is the risk factor for AMS. T11613C, A8923G, and T5543C are protective factors for AMS. The role of A8923G mutation may correlate with the sodium and water balance and the role of the A4576G mutation may be related to the disability to maintain blood oxygen level after quickly entering the plateau.

Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults

BackgroundWe evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and in healthy lowlanders 40 years of age or older.MethodsTrial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo, starting 24 hours before staying for 2 days at 3100 m. The mean (±SD) age of participants was 57±9 years, and 34% were women. At 760 m, COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater, arterial partial pressure of carbon dioxide less than 45 mm Hg, and mean forced expiratory volume in 1 second of 63±11% of predicted. The primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE) at 3100 m. Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. Trial 2 comprised 345 healthy lowlanders. Their mean age was 53±7 years, and 69% were women. The participants in trial 2 underwent the same protocol as did the patients with COPD in trial 1. The primary outcome in trial 2 was the incidence of AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating AMS).ResultsIn trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHE (hazard ratio, 0.54; 95% confidence interval [CI], 0.37 to 0.79; P<0.001). The number needed to treat (NNT) to prevent one case of ARAHE was 4 (95% CI, 3 to 8). In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (hazard ratio, 0.48; 95% CI, 0.29 to 0.80; chi-square statistic P=0.035). The NNT to prevent one case of AMS was 10 (95% CI, 5 to 141). No serious adverse events occurred in these trials.ConclusionsPreventive treatment with acetazolamide reduced the incidence of adverse altitude effects requiring an intervention in patients with COPD and the incidence of AMS in healthy lowlanders 40 years of age or older during a high-altitude sojourn. (Funded by the Swiss National Science Foundation [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung], Lunge Zürich, and the Swiss Lung Foundation; ClinicalTrials.gov numbers, NCT03156231 and NCT03561675.)

A novel echocardiographic parameter to identify individuals susceptible to acute mountain sickness

BackgroundAcute mountain sickness (AMS) may cause life-threatening conditions. This study aimed to screen echocardiographic parameters at sea level (SL) to identify predictors of AMS development. MethodsOverall, 106 healthy men were recruited at SL and ascended to 4100 m within 7 days by bus. Basic characteristics, physiological data, and echocardiographic parameters were collected both at SL and 4100 m above SL. AMS was identified by 2018 Lake Louise Questionnaire Score. ResultsAfter acute high altitude exposure (AHAE), 33 subjects were diagnosed with AMS and exhibited lower lateral mitral valve tissue motion annular displacement (MV TMADlateral) at SL than AMS-free subjects (13.09 vs. 13.89 mm, p = 0.022). MV TMADlateral at SL was significantly correlated with AMS occurrence (OR = 0.717, 95% CI: 0.534–0.964, p = 0.028). The MV TMADlateral<13.30-mm group showed over 4-fold risk for AMS development versus the MV TMADlateral≥13.30-mm group. After AHAE, the MV TMADlateral<13.30-mm group had increased HR (64 vs. 74 bpm, p = 0.001) and right-ventricular myocardial performance index (0.54 vs. 0.69, p = 0.009) and decreased left ventricular global longitudinal strain (−21.50 vs. −20.23%, p = 0.002), tricuspid valve E/A ratio (2.11 vs. 1.89, p = 0.019), and MV E-wave deceleration time (169.60 vs. 156.90 ms, p = 0.035). ConclusionMV TMADlateral at SL was a potential predictor of AMS occurrence and might be associated with differential alterations of ventricular systolic and diastolic functions in subjects with different MV TMADlateral levels at SL after AHAE.

Comparing Acute Mountain Sickness Definitions to Examine Differences in Systemic Inflammation

Acute mountain sickness (AMS) occurs when individuals rapidly ascend to high altitudes, but its exact cause remains unknown. Additionally, AMS is assessed using a subjective questionnaire with a variety of criteria used for diagnosis so there is no precise, objective method for determining if a subject has AMS. Hypoxia, or low oxygen, at altitude results in a proinflammatory state and AMS is associated with systemic inflammation as determined by elevated plasma levels of some cytokines. Thus, we wanted to determine if the association between AMS and inflammation was altered based on how AMS was defined. To examine this, 17 women and 17 men were exposed to 10 hours of normobaric hypoxia (11.5% O2) simulating 15600 feet. Blood samples taken before and at 10 hours of hypoxia were assayed for 13 inflammatory cytokines. AMS was defined by the following definitions: 1) Lake Louise Questionnaire (LLQ) score ≥3 and a headache score ≥1 at the 10-hour time point, 2) maximum LLQ score ≥3 and a maximum headache score of ≥1, 3) maximum LLQ score ≥3 and a maximum Environmental Symptoms Questionnaire (ESQ) score of 0.7 or maximum LLQ ≥3, a maximum headache score ≥2, and a maximum ESQ ≥0.4, 4) maximum LLQ ≥3, 5) LLQ score ≥3 at the 10-hour time point. We found that Interleukin (IL) 8 significantly increased in AMS- but not AMS+ participants regardless of AMS definition. Additionally, AMS- but not AMS+ participants significantly increased IL-1β and IL-33 concentration from baseline to 10 hours of hypoxia under only three out of the five definitions (#1, #3 & #5 above for IL-1β and #3, #4, & #5 above for IL-33). Furthermore, the change in IL-1β concentration after 10 hours of hypoxia was significantly different between AMS- and AMS+ participants under definition #3 above. These data suggest that how AMS is defined may influence whether or not there are differences in circulating inflammatory cytokines between those with and without AMS. Therefore, the relationship between systemic inflammation and AMS may be more complex than previously thought.

Low Stroke Volume Index in Healthy Young Men Is Associated with the Incidence of Acute Mountain Sickness after an Ascent by Airplane: A Case-Control Study.

Background The aims of this study were to explore the characteristics of left ventricular (LV) functional changes in subjects with or without acute mountain sickness (AMS) and their associations with AMS incidence. Methods A total of 589 healthy men were enrolled and took a trip from Chengdu (500 m, above sea level (asl)) to Lhasa (3700 m, asl) by airplane. Basic characteristics, physiological data, and echocardiographic parameters were collected both at Chengdu and Lhasa, respectively. AMS was identified by the Lake Louise Questionnaire Score. Results The oxygen saturation (SpO2), end-systolic volume index, end-diastolic volume index (EDVi), stroke volume index (SVi), E-wave velocity, and E/A ratio were decreased, whereas the heart rate (HR), ejection fraction, cardiac index (CI), and A-wave velocity were increased at the third day after arrival, as evaluated by an oximeter and echocardiography. However, AMS patients showed higher HR and lower EDVi, SVi, CI, E-wave velocity, and E/A ratio than AMS-free subjects. Among them, SVi, which is mainly correlated with the changes of EDVi and altered LV filling pattern, was the most valuable factor associated with AMS incidence following receiver-operator characteristic curves and linear and Poisson regression. Compared with subjects in the highest SVi tertile, subjects in the middle SVi tertile showed higher multivariable Incidence Rate Ratios (IRR) for AMS with higher incidences of mild headache and gastrointestinal symptoms, whereas subjects in the lowest SVi tertile showed even higher multivariable IRR with higher incidences of all the symptoms. Conclusions This relatively large-scale case-control study revealed that the reduction of SVi correlated with the altered LV filling pattern was associated with the incidence and clinical severity of AMS.

The Magnitude of Diving Bradycardia During Apnea at Low-Altitude Reveals Tolerance to High Altitude Hypoxia.

Acute mountain sickness (AMS) is a potentially life-threatening illness that may develop during exposure to hypoxia at high altitude (HA). Susceptibility to AMS is highly individual, and the ability to predict it is limited. Apneic diving also induces hypoxia, and we aimed to investigate whether protective physiological responses, i.e., the cardiovascular diving response and spleen contraction, induced during apnea at low-altitude could predict individual susceptibility to AMS. Eighteen participants (eight females) performed three static apneas in air, the first at a fixed limit of 60 s (A1) and two of maximal duration (A2–A3), spaced by 2 min, while SaO2, heart rate (HR) and spleen volume were measured continuously. Tests were conducted in Kathmandu (1470 m) before a 14 day trek to mount Everest Base Camp (5360 m). During the trek, participants reported AMS symptoms daily using the Lake Louise Questionnaire (LLQ). The apnea-induced HR-reduction (diving bradycardia) was negatively correlated with the accumulated LLQ score in A1 (rs = −0.628, p = 0.005) and A3 (rs = −0.488, p = 0.040) and positively correlated with SaO2 at 4410 m (A1: r = 0.655, p = 0.003; A2: r = 0.471, p = 0.049; A3: r = 0.635, p = 0.005). Baseline spleen volume correlated negatively with LLQ score (rs = −0.479, p = 0.044), but no correlation was found between apnea-induced spleen volume reduction with LLQ score (rs = 0.350, p = 0.155). The association between the diving bradycardia and spleen size with AMS symptoms suggests links between physiological responses to HA and apnea. Measuring individual responses to apnea at sea-level could provide means to predict AMS susceptibility prior to ascent.

Prophylactic Acetaminophen or Ibuprofen Result in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial

Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed.

Optic Nerve Sheath Diameter Increase on Ascent to High Altitude: Correlation With Acute Mountain Sickness.

Elevated optic nerve sheath diameter on sonography is known to correlate with increased intracranial pressure and is observed in acute mountain sickness. This study aimed to determine whether optic nerve sheath diameter changes on ascent to high altitude are associated with acute mountain sickness incidence. Eighty-six healthy adults enrolled at 1240 m (4100 ft), drove to 3545 m (11,700 ft) and then hiked to and slept at 3810 m (12,500 ft). Lake Louise Questionnaire scores and optic nerve sheath diameter measurements were taken before, the evening of, and the morning after ascent. The incidence of acute mountain sickness was 55.8%, with a mean Lake Louise Questionnaire score ± SD of 3.81 ± 2.5. The mean maximum optic nerve sheath diameter increased on ascent from 5.58 ± 0.79 to 6.13 ± 0.73 mm, a difference of 0.91 ± 0.55 mm (P = .09). Optic nerve sheath diameter increased at high altitude regardless of acute mountain sickness diagnosis; however, compared to baseline values, we observed a significant increase in diameter only in those with a diagnosis of acute mountain sickness (0.57 ± 0.77 versus 0.21 ± 0.76 mm; P = .04). This change from baseline, or Δ optic nerve sheath diameter, was associated with twice the odds of developing acute mountain sickness (95% confidence interval, 1.08-3.93). The mean optic nerve sheath diameter increased on ascent to high altitude compared to baseline values, but not to a statistically significant degree. The magnitude of the observed Δ optic nerve sheath diameter was positively associated with acute mountain sickness diagnosis. No such significant association was found between acute mountain sickness and diameter elevation above standard cutoff values, limiting the utility of sonography as a diagnostic tool.

Long-Term Monitoring of Oxygen Saturation at Altitude Can Be Useful in Predicting the Subsequent Development of Moderate-to-Severe Acute Mountain Sickness

The use of pulse oximetry (Spo2) to identify subjects susceptible to acute mountain sickness (AMS) is the subject of debate. To obtain more reliable data, we monitored Spo2 for 24 hours at altitude to investigate the ability to predict impending AMS. The study was conducted during the climb from Alagna (1154 m) to Capanna Regina Margherita (4559 m), with an overnight stay in Capanna Gnifetti (3647 m). Sixty subjects (11 women) were recruited. Each subject was fitted with a 24-hour recording finger pulse oximeter. The subjects rode a cable car to 3275 m and climbed to 3647 m, where they spent the night. In the morning, 24 subjects (6 women) had a Lake Louise Questionnaire score (LLS) ≥ 3 (AMS(+)), and 15 subjects (4 women) exhibited moderate-to-severe disease (LLS ≥ 5 = AMS(++)). At Alagna, Spo2 did not differ between the AMS(-) and AMS(+) subjects. At higher stations, all AMS(+) subjects exhibited a significantly lower Spo2 than did the AMS(-) subjects: at 3275 m, 85.4% vs 87.7%; resting at 3647 m, 84.5% vs 86.4%. The receiver operating characteristics curve analysis resulted in a rather poor discrimination between the AMS(-) subjects and all of the AMS(+) subjects. With the cutoff LLS ≥ 5, the sensitivity was 86.67%, the specificity was 82.25%, and the area under the curve was 0.88 (P < .0001) for Spo2 ≤ 84% at 3647 m. We conclude that AMS(+) subjects exhibit a more severe and prolonged oxygen desaturation than do AMS(-) subjects starting from the beginning of altitude exposure, but the predictive power of Spo2 is accurate only for AMS(++).

241 Echocardiographic Assessment of Myocardial Performance in Response to High Altitude and Development of Subclinical Pulmonary Edema in Healthy Climbers

Despite a known association with increased pulmonary artery pressure (PAP), the pathophysiology of high-altitude pulmonary edema (HAPE) remains incompletely understood. Data regarding the impact of high altitude on left and right heart functions are sparse and conflicting. No single parameter has been validated to predict the development of HAPE among recreational climbers. We aimed to assess, by echocardiography, the right and left ventricular responses to high-altitude-induced hypoxia and to detect the occurrence of subclinical pulmonary edema. This observational study included 14 healthy subjects (8 men ; ages 27-65 years old) participating in a trekking expedition in the Everest Valley, Nepal. Echocardiography, using a portable unltrasound system (Vivid I, GE Healthcare), including the assessment of right ventricular performance parameters, was performed in Montréal (30 meters above sea level), Namche Bazar, Nepal (3450m) and Chhukkung (4730m). Lung ultrasound was performed to detect the appearance of ultrasound lung comets (ULCs) suggestive of subclinical pulmonary edema, quantified by a previously validated ULC score integrating the extent and severity of lung comets. Symptoms of high altitude sickness were assessed via the validated Lake Louise Questionnaire (LLQ). At high altitude, ULCs were seen in all except one of the subjects, with ULC scores ranging from 0 to 18 at 4730m (Fig. 1). None of the subjects had clinical criteria for HAPE. Systolic PAP increased in all subjects between Montréal and Chhukkung (mean PAP 27.4 +/− 5.4 mmHg vs. 39.3 +/− 7.7 mmHg respectively; p<0.001). Right ventricular myocardial performance index (MPI; Tei index), assessed by the pulsed-wave doppler method, increased with rising altitude (0.32 +/− 0.08 at 30m vs. 0.41 +/− 0.10 at 4730m; p=0.046). The right ventricular parameters S' and Tricuspid Annular Plane Systolic Excursion (TAPSE) remained unchanged, as did the left ventricular E/A ratio suggesting no significant change in left ventricular diastolic function. Heart rate and cardiac output increased in every subject at high altitude. No correlation could be drawn between PAP increment and MPI, MPI and ULC score, and MPI and LLQ score. Subclinical high-altitude pulmonary edema is frequent in healthy climbers living at low altitude. Right ventricular MPI increases at high altitude, and does not seem to be correlated to the magnitude of PAP increment. Whether rising MPI is a physiologic adaptive mechanism to high-altitude hypoxia or a pathologic response identifying HAPE-susceptible subjects needs to be further determined.

The effect of hypohydration severity on the physiological, psychological and renal hormonal responses to hypoxic exercise

Evidence of the effect of dehydration on physiological responses to hypoxia is limited. The purpose of this study was to determine the effect of hypohydration severity on physiological, renal hormonal and psychological responses to acute hypoxia. Eight males completed intermittent walking tests under normobaric hypoxic conditions (FI O(2) = 0.13) after completing four separate hypohydration protocols, causing change in body mass of approximately 0% (EU), -1% (H1), -2% (H2) and -3% (H3). Physiological and psychological markers were monitored throughout the 125 min test. Fluid controlling hormones were measured pre and post exposure. Heart rate, core temperature, peripheral arterial oxygen saturation (SpO(2)), minute ventilation and urine osmolality were found to be significantly different between hydration conditions and correlated with Lake Louise Questionnaire score (LLQ) (P < 0.05). LLQ score increased with hypohydration severity above H2 (EU 1.3 +/- 1; H1 1.2 +/- 1; H2 2.7 +/- 2; H3 3.9 +/- 2) (P < 0.001). Antidiuretic hormone and aldosterone increased over the test, but were not different between hydration conditions (P < 0.05). Atrial natriuretic peptide showed no change over time, or with conditions. Therefore, renal hormones are not influenced by hypohydration severity during moderate intensity hypoxic exercise. Hypohydration less than -2% induces greater physiological strain during hypoxic exercise and may cause rise in symptoms such as, fatigue, headache, nausea and lightheadedness.

Prevalence of Acute Mountain Sickness among Finnish Trekkers on Mount Kilimanjaro, Tanzania: An Observational Study

The aim of this study was to evaluate the prevalence of acute mountain sickness (AMS) among trekkers on Mount Kilimanjaro during the winter season of 2006-2007. A A total of 130 Finnish trekkers at Marungu route were asked to complete daily a Lake Louise self-report and clinical assessment score questionnaire with the help of a trainee Finnish guide during their trek to Kilimanjaro. A Lake Louise questionnaire score>or=3 indicated AMS. Altogether 112 mountaineers or travelers [54 men, 58 women, mean age 51+/-10 (SD) years] were studied. Fifty-nine travelers (53%) reached Gillman's Point or Uhuru Peak. The incidence of AMS among Finnish Kilimanjaro trekkers was 75%. The most common high altitude symptoms were headache, followed by sleeping problems and fatigue or weakness. The incidence of AMS is high among trekkers climbing Mount Kilimanjaro.The main reason for this seems to be rapid ascent. Kilimanjaro treks normally have a fixed timetable, and for commercial reasons there is little opportunity to spend extra days for acclimatization in the camps. Some contributing factors are preventable, so we recommend an educational program for all the trekking agencies that guide on this peak and, in particular, the Tanzania-based guiding agencies, which, typically, are driving these very fast ascent rates.