Clinical Effect of Descent in Infants with Bronchiolitis Diagnosed at Altitude: A Prospective Multicenter Study

Abstract

Poirier, Anne, Amélie Basso, Sarah Bonnet-Ducrot, Ellen Katranji, Sophia Cherif-Alami, Sophie Chateigner-Coelsch, Manon Navarre, Cécile Ricard, and Corentin Tanné. Clinical effect of descent in infants with bronchiolitis diagnosed at altitude: a prospective multicenter study. High Alt Med Biol. 26:134–139, 2025.

Objective:

This study aims to assess the clinical impact of descending to a lower altitude in infants with bronchiolitis diagnosed at an altitude above 1,000 m.

Methods:

We performed a prospective, observational, multicenter study during two consecutive winters (2022–2023 and 2023–2024). The diagnosis was made by local general practitioners (GPs) who then sent the patients who were younger than 1 year and had a Wang respiratory score (WRS) ≥4 to any of the five emergency departments (EDs) located at lower altitudes. The WRS, peripheral oxygen saturation (SpO₂), and respiratory rate (RR) recorded by the GPs and at the EDs were compared.

Results:

We included 74 infants (59% females, median age 5.4 [3.6–8.0] months). Compared with the median values recorded by the GPs at altitudes above 1,000 m, the median values at the lower-altitude EDs were significantly better for the WRS (5.0 vs. 6.0, p = 0.002), RR (50/min vs. 60/min, p = 0.001), and SpO₂ (97.0% vs. 91.5%, p < 0.001).

Conclusion:

Descending to a lower altitude significantly improved respiratory function in infants younger than 1 year with bronchiolitis diagnosed at altitudes above 1,000 m.

Introduction

Overall, 52.8 million skiers visit French ski resorts every year (Vanat, 2020), chiefly in the Alpine districts of Haute-Savoie, Savoie, and Isère, causing a sharp rise in population during the winter months. Many skiers travel as families, and the skiing season coincides with the bronchiolitis season (Cassibba and Mortamet, 2021). Acute bronchiolitis is the most common medical emergency in infants younger than 1 year of age (Snow et al., 2024), and general practitioners (GPs) with offices in ski resorts therefore see many infants with bronchiolitis (Li et al., 2019). GPs in the French Alps can request transport to a local community hospital or regional university hospital if warranted by the severity of the respiratory impairment.

The Wang Respiratory Score (WRS) assesses bronchiolitis severity based on the respiratory rate (RR), wheezing, chest retractions, and general condition (Wang et al., 1992). A WRS above 4 warrants transfer to a hospital emergency department (ED) (Chin and Seng, 2004) and standardized treatment (Milési et al., 2023).

Few data are available on the impact of altitude on bronchiolitis severity. A retrospective study analyzed data from infants with bronchiolitis sent from ski resorts to the Albertville hospital in the French Alps over two winter seasons (Jean, 2019). Of the 28 infants, 19 had respiratory disease onset before the trip to the ski resort, indicating insufficient information of parents about the hazards of taking infants with respiratory symptoms to higher altitudes. Median age was 8.9 [1.5–33.0] months. Mean peripheral oxygen saturation (SpO₂) was 87% when the infants were first assessed at the ski resort and 92% upon arrival at the hospital located at an altitude of only 352 m. In a database study, the percentage of infants who required admission for respiratory syncytial virus (RSV) bronchiolitis increased with increasing altitude and was greatest above 2,500 m (Choudhuri et al., 2006). Higher altitude was associated with lower SpO₂ values and with worse nasal obstruction and ciliary activity impairment. The drier air at higher altitudes is known to adversely affect mucociliary function, thereby decreasing respiratory-secretion clearance (Rodway and Windsor, 2006). Moreover, the lower oxygen content of air with increasing altitude may induce pulmonary vasoconstriction, leading to an increase in vascular permeability with pulmonary congestion, notably in patients with viral respiratory infections. Taking infants to higher altitudes during active viral respiratory infections is inadvisable (Tanné et al., 2023). We are not aware of prospective studies assessing the clinical changes seen when infants with bronchiolitis diagnosed at moderate or high altitudes are taken to lower altitudes.

The aim of this prospective observational multicenter study was to evaluate the changes in bronchiolitis severity seen in infants younger than 1 year who had moderate-to-severe bronchiolitis diagnosed while at a ski resort and were then transferred to hospitals at lower altitudes.

Methods

Study design and patients

We conducted a prospective, observational, multicenter study in patients seen by GPs who worked in French Alpine ski resorts and belonged to the Mountain-Community General Practitioners nonprofit organization (Association des Médecins de Montagne, MDEM) designed to collect data and improve physician training.

The study promoter was the Chambéry hospital (Centre Hospitalier Métropole Savoie, CHMS) and the protocol was approved by the Savoie Mont Blanc University ethics committee (#2022-26-ALTIB). Informed consent was obtained from the parents or guardian(s) before study inclusion. Parents or guardian(s) were told that they could stop study participation at any time without specifying the reason and without jeopardizing the care to the child.

Inclusion criteria were age younger than 1 year at diagnosis, diagnosis of bronchiolitis in 2022–2023 or 2022–2023 by a GP in a ski resort located at an altitude of more than 1,000 m, WRS ≥4 during the GP visit, and transfer to the ED of any of the five nearby hospitals with pediatric units located at altitudes of less than 1,000 m. The five participating hospitals included four local and regional hospitals located in Chambéry (270 m), Sallanches (550 m), Albertville (352 m), and Bourg Saint Maurice (860 m), respectively, and one university hospital in Grenoble (212 m). In France since September 2023, i.e., between the two study seasons, the long-acting monoclonal antibody nirsevimab against the respiratory syncytial virus is routinely administered to neonates whose parents have given informed consent (Drysdale et al., 2023). Consecutive patients meeting all inclusion criteria were enrolled in the study.

Data collection

The altitudes of each GP office and ED were collected. The WRS, RR, and SpO₂ for each patient were recorded by the GP who requested ED admission and by the ED physicians. The primary outcome was the WRS change between the GP office and the ED. The secondary outcomes were the changes in RR and SpO₂ between the GP office and the ED.

Before the study, the participating GPs received a fact sheet and video tutorial on a procedure for clearing the upper respiratory tract in infants. After using this procedure, each GP recorded the WRS, RR, and SpO₂ according to their usual practice. Transport to the ED was arranged by the GP as appropriate for the patient’s clinical condition and according to local habits. Data on transport modalities or clinical parameters during transportation were not collected. The GP communicated the values of the clinical variables to the ED.

At ED arrival, the upper respiratory tract was cleared and the WRS, RR, and SpO₂ were recorded. Other recorded variables were age; sex; gestational age; medical history; whether the patient was a local ski-community resident or a visitor and, in the latter case, time since arrival at the ski resort; time since symptom onset; and whether the patient was admitted, discharged to the initial altitude, or discharged to a lower altitude.

Statistical analysis

The primary outcome was the change in the WRS from the GP value to the ED value. To detect a WRS decrease of 0.5, indicating a clinically relevant change, 73 patients were needed (0.05 alpha risk, 80% power).

Quantitative variables were described as median [interquartile range] and qualitative variables as n (%). The WRS values recorded by the GPs and at the EDs were compared by applying the paired Wilcoxon test.

We then sought to identify factors significantly associated with a change in bronchiolitis severity after the descent to a lower altitude. To this end, we categorized the patients as having mild, moderate, or severe bronchiolitis, defined as WRS values upon ED arrival of 0–3, 4–7, or 8–14, respectively. We then used to identify factors associated with a change from one category to a lower category by univariate analysis (khi-2, Wilcoxon–Mann–Whitney, and Fisher’s exact tests). We also planned a multivariate analysis (logistic regression) of factors associated with p values by univariate analysis.

Missing data were counted and reported but ignored in the statistical analyses.

All tests were two-sided and p values lower than 0.05 were taken to indicate significant differences. All statistical tests were carried out using the R.4.3.0 program (httsp://www.r-project.org).

Results

The GPs included 74 infants, 48 during the first and 26 during the second winter season. ED data were available for all patients included by GPs. Table 1 reports their main features.

Table 1.

Characteristics of the Study Patients

Characteristics	n (%) or median [IQR]
Sex, n (%)
Male	30 (41.0)
Female	44 (59.0)
Age (months)	5.36 [3.6–8.0]
Gestational age (weeks)	40.0 [39.0–40.0]
Missing data	19
Medical history
Respiratory disease^a	18 (24.3)
Heart disease^b	2 (2.7)
Other^c	7 (9.5)
No known previous disease	47 (63.5)
Place of residence
Local resident	45 (60.8)
Visitor	29 (39.2)
Altitude of the GP offices (meters)	1,500 [1,103–1,810]
Altitude decrease from GP offices to EDs	1,164 [604–1,573]
Days since respiratory-symptom onset
≤3	50 (67.6)
4–7	2 (2.7)
≥8	17 (22.9)
Unknown	5 (6.8)
Days at high altitude in visitors (n = 29)
≤3	10 (34.5)
4–7 days	4 (13.8)
≥8	3 (10.3)
Unknown	12 (41.4)

One patient had hyaline membrane disease with pulmonary hypertension and 17 had a history of one or more episodes of bronchiolitis or asthma.

One patient had ventricular septal defect and another an unspecified valvulopathy.

Other: Down syndrome, medium-chain acyl-coA dehydrogenase deficiency, eczema, intrauterine growth retardation, craniostenosis, adrenal insufficiency, prematurity.

ED, emergency department; GP, general practitioner; IQR, interquartile range.

Of the 29 patients who were not ski-community residents, 10 did and 10 did not have respiratory symptoms before traveling to the ski resort; this information was missing for the remaining 9 patients. Of the 74 patients, 53 (71.6%) were hospitalized, 11 (14.9%) were discharged to the place of usual or temporary residence in the ski community, and 10 were discharged to their usual place of residence at low altitude.

Primary outcome

Fig. 1A shows the box plots of the WRS values. The overall median value decreased significantly from 6.0 [5.5–6.0] in the GP offices to 5.0 [5.0–7.0] in the EDs (p = 0.002). After the descent, the WRS decreased in 29 (39.0%) patients and increased in 8 (11.0%) patients. Table 2 reports the numbers of patients in each of the three WRS categories.

FIG. 1.

(A) Box plots of the Wang Respiratory Score values measured at the GP offices (left) and EDs (right). (B) Box plots of the RR values (breaths/minute) measured at the GP offices (left) and EDs (right). (C) Box plots of the SpO₂ values measured at the GP offices (left) and EDs (right). ED, emergency department; GP, general practitioner; RR, respiratory rate, in breaths per minute; SpO₂, peripheral oxygen saturation, as the % of oxyhemoglobin over hemoglobin; WRS, Wang Respiratory Score, which can range from 0 to 12.

Table 2.

Bronchiolitis Severity as Assessed by the GPs and ED Physicians

Wang Respiratory Score	GP	ED
0–3: mild^a	0 (0)	17 (23.0)
4–7: moderate	50 (67.6)	42 (56.7)
8–14: severe	24 (32.4)	15 (20.3)
RR, breaths/min, median [IQR]	60 [50–60]	50 [40–58]
Missing data	8	0
SpO₂, %, median [IQR]	91.5 [87.8–94.0]	97.0 [95.0–99.0]
Missing data	20	0

A Wang Respiratory Score of at least 4 during the general practitioner assessment was required for study inclusion.

RR, respiratory rate; SpO₂, peripheral oxygen saturation.

Secondary outcomes

The secondary outcomes were the changes in RR and SpO₂ values after the descent from the GP office to the ED. The box plots for RR and SpO₂ are shown in Fig. 1B and C, respectively, and the overall changes in median values are reported in Table 2. The overall median RR decreased significantly after the descent from 60 [50–60] to 50 [40–58] (p = 0.001). After the descent, the RR decreased in 36 patients, remained unchanged in 20 patients, and increased in 10 patients; the GP value was missing for 8 patients. The overall median SpO₂ value increased significantly after the descent from 91.5% [87.8–94.0] to 97.0% [95.0–99.0] (p < 0.001). SpO₂ increased in 33 patients, remained unchanged in 16 patients, and worsened in 5 patients; the GP value was missing for 20 patients.

Evaluation of factors potentially associated with improvement after descent

By univariate analysis, the only factor significantly associated with a WRS improvement after the descent was a worse WRS value before the descent (p < 0.001). Age, sex, gestational age, medical history, and altitude difference between the GP office and ED were not significantly associated with the WRS change. Given the results of the univariate analysis, the planned multivariate analysis was not performed.

Discussion

This prospective study of infants younger than 1 year who were diagnosed with bronchiolitis with a WRS of at least 4 while at an altitude of at least 1,000 m showed that descending to a lower altitude was followed by significant improvements in the WRS, RR, and SpO₂ values. The only factor significantly associated with the WRS improvement after the descent was the initial WRS value at the higher-altitude GP office.

The hazards associated with taking infants with upper respiratory infections to high altitudes have been highlighted previously (Jean, 2019; Yaron and Niermeyer, 2008). A survey of physicians working in ski communities in the French Alps showed that 94 (90%) of the 104 respondents advised against taking infants with upper respiratory infections to higher altitudes and reported recommending attention to hydration, air humidification, and protection against the cold (Tanné et al., 2023). With increasing altitude, barometric pressure decreases, diminishing the partial pressure of inspired oxygen and potentially promoting hypoxemia in patients with respiratory disease (De Meer et al, 1995). The lower humidity, colder temperatures, and lower oxygen content of air at high altitudes impair mucociliary function and, therefore, airway secretion clearance (Rodway and Windsor, 2006). Moreover, the nasal obstruction often caused by cold temperatures results in mouth breathing, bypassing the humidification and warming that occurs with nose breathing. A review of 81 studies of bronchiolitis in infants younger than 2 years found that living at an altitude greater than 2,500 was associated with greater disease severity. Of note, three-fifths of our patients were permanent ski-community residents. The interquartile age range in our cohort [3.6–8.0] suggests that most patients followed the usual advice to refrain taking babies younger than 3 months to high altitudes.

Our findings are consistent with the sparse published data on the effects of altitude in patients with bronchiolitis. A prospective cohort study done in infants with bronchiolitis seen at any of 30 EDs identified associations linking higher altitude to worse chest retractions (odds ratio, 1.6; 95% confidence interval, 1.1–2.1; p < 0.001) and decreased air entry (2.0; 1.6–2.6; p < 0.001) (Wang and Cavagnaro, 2012). Both hypoxemia and mortality have been reported to be more common at high than low altitudes in young children with acute lower respiratory infections (Yaron and Niermeyer, 2008). Median SpO₂ in our study increased by 5.5% after descending to a lower altitude. It thus seems reasonable to suggest that infants seen at EDs for bronchiolitis should not return to a higher altitude until their clinical condition has resolved.

In our study, the number of patients decreased by nearly a half between the first and the second season of the study period. This decrease may be ascribable to the introduction in France between the two seasons of routine nirsevimab injection to neonates whose parents consent, the goal being to decrease the risk of RSV, a major cause of bronchiolitis in infants. In a database study, nirsevimab substantially reduced infant hospitalizations for lower respiratory-tract infections due to RSV (Ares-Gómez et al., 2024). A difference in weather patterns may also have been involved, but we did not assess this point.

SpO₂ has been found to be a reliable objective marker for bronchiolitis severity (Baraldi et al., 2014). SpO₂ values in healthy individuals decrease with increasing altitude. The SpO₂ target in patients treated for bronchiolitis may deserve to be adjusted according to altitude. In Bogota, a city at 2,625 m, using a target of 85% instead of the 90% value recommended by the American Academy of Pediatrics (American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis, 2006) to decide when infants with bronchiolitis can be discharged from hospital to home produced good outcomes and lowered costs (Rodriguez-Martinez et al., 2022). The UK NICE and SIGN recommends a target ≥92% (normoxia) (Caffrey Osvald and Clarke, 2016). In a randomized controlled trial in infants with bronchiolitis, targeting 90% vs. 94% produced similar results regarding the primary outcome of time to cough resolution, with no significant differences in adverse events (Cunningham et al., 2015). The optimal SpO₂ target for infants who return to altitude after discharge is unknown.

Importantly, pediatric oximeters are not used by all GPs in France. Thus, of our 74 patients, 20 (27%) did not have their SpO₂ measured by the GP. Awareness should be raised among GPs, notably those working at altitudes, of the usefulness of using oximeters. In addition to respiratory scores, SpO₂ may also be of use for determining which patients should be transferred to the ED.

One limitation of our study is that, despite the prospective design, data on RR and SpO₂ during the GP visit were missing for 8 (11%) and 20 (27%) patients, respectively. Second, the sample size was small. However, the demonstration of significant differences for the primary and secondary outcomes despite this small size supports the validity of the effect of going to a lower altitude. Third, although the GPs were asked to include consecutive eligible patients, the GP workload in ski resorts is extremely heavy in winter and lack of time may have precluded the enrolment of some patients. We do not know how many eligible patients were not included. This explains the absence of a patient flowchart. Fourth, we did not have a low-altitude control group composed of infants who had bronchiolitis diagnosed at low altitude and were sent to an ED based on a WRS ≥4. Fifth, three-fifths of our patients were ski-community residents and may therefore have been living permanently at altitudes above the ski resort where the GP office was located. The overall altitude decrease in any such patients would have been underestimated. Also, acclimatization to altitude in ski-community residents may have affected the response to descent compared with that of the visitors. Sixth, we did not collect the transport time, which may, in addition to the altitude difference, have influenced the effect of the descent on respiratory function. Seventh, we chose the WRS as the primary outcome. Although the WRS has shown high interobserver agreement, better performance has been reported for the Kristjansson Respiratory Score and modified Tal score (Pinto et al., 2020). Finally, the patient recruitment conducted only in the French Alps may limit the general applicability of our findings.

Conclusion

Infants younger than 1 year of age in whom acute bronchiolitis with a WRS ≥4 is diagnosed at an altitude above 1,000 m often experienced improvements in respiratory function after being taken to a lower altitude. This finding in a small sample with no low-altitude control group warrants further studies of infants with bronchiolitis designed to clarify the effects of descending to a lower altitude, as well as to determine the safe altitude to which discharged infants can be returned. Our study also supports the wisdom of avoiding travel to high altitude with young infants who already have upper respiratory-tract symptoms or a history of bronchiolitis episodes.

Footnotes

Authors’ Contributions

Conceptualization: A.P. and C.T. Data curation: A.P., C.R., and C.T. Formal analysis: A.P., C.R., and C.T. Investigation: A.P., A.B., S.B.D., E.K., S.C.A., S.C.C., and C.T. Methodology: A.P., C.R., and C.T. Project administration: C.T. Resources: A.P. and C.T. Software: A.P. and C.R. Supervision: C.T. Validation: A.P., A.B., S.B.D., E.K., S.C.A., S.C.C., M.N., C.R., and C.T. Visualization: C.T. Writing—original draft: A.P. Writing—review and editing: C.T.

Data Sharing Statement

The data collected and analyzed for this study will be shared with other investigators upon reasonable request to the corresponding author.

Author Disclosure Statement

None of the authors has any conflicts of interest to disclose.

Funding Information

No funding was received for this article.

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