# Cold-Air Inhalation Safety Evidence

> Human cold-air inhalation safety evidence for AIRCHILL: 39-study systematic review, large population challenges, current CLARINET trial, airway physiology, epithelial stress, cilia evidence and the remaining clinical saf…

- Canonical: https://www.medicalcooling.com/cold-air-safety/
- Markdown: https://www.medicalcooling.com/cold-air-safety/index.md
- Language: en-US
- Last modified: 2026-08-23T22:39:24+00:00

Airway safety evidence · reviewed 23 August 2026

# Cold air has already been inhaled by thousands of people in clinical research.

That gives AIRCHILL a substantial external human safety foundation for short, supervised cold-air exposure. It does not yet establish the safety of prolonged endotracheal respiratory cooling in critically ill patients. The strongest known acute risk is predictable bronchoconstriction in susceptible airways; the most important remaining gaps are prolonged lower-airway exposure, mucociliary function, secretion handling and emergency-patient validation.

[39-study register](#study-register)[AIRCHILL evidence](https://www.medicalcooling.com/evidence/)[Clinical study planner](https://www.medicalcooling.com/clinical-study-planner/)

Safety verdict

## Good short-exposure evidence. Promising prolonged preclinical evidence. Patient safety still needs to be shown.

Substantial human evidence39 studies
A 2026 peer-reviewed systematic review found that cold-air challenge could be performed without major adverse events. The majority of studies did not report severe symptoms.

Derived study count≥1,778
Participants across the 39 studies when the reported study samples are summed. Many underwent more than one challenge, so the number of cold-air exposures is higher.

Large population precedent7,248
German schoolchildren underwent cold-air challenge in the 1993 Nicolai/von Mutius population study. This cohort is separate from the 39-study diagnostic review and should not be added to it as if all subjects were unique.

AIRCHILL gap0
Critically ill or emergency patients have yet been prospectively studied with AIRCHILL endotracheal cold-air ventilation. Clinical safety therefore remains a validation objective.

What “no major adverse events” means here
It does not mean cold air is physiologically inert. Many studies deliberately used cold dry air to provoke bronchoconstriction. Reported effects include cough, dyspnoea, wheeze, chest tightness, dry mouth and occasional severe cough. In asthma and exercise-induced bronchoconstriction, a fall in FEV1 was often the intended endpoint. For AIRCHILL, this makes bronchospasm and airway resistance a known, monitorable safety hazard rather than an unknown one.

Highest-level evidence

## The 2026 systematic review is the anchor.

Marain and colleagues screened 842 unique records, reviewed 79 full texts and included 39 cold-air challenge studies, 19 of them in meta-analysis. Across the included literature, 18 studies reported no effect on lung function in healthy controls, while 27 found a significant cold-air effect in asthma. The authors concluded that cold-air challenge can be executed without major adverse events, with symptomatic challenges consistent with bronchoconstriction.

Healthy airways
### Often little measurable obstruction

18 of 39 papers stated that cold-air hyperventilation did not affect lung function of healthy controls. This is reassuring for short exposures but does not address prolonged intubated ventilation.

Susceptible airways
### Bronchoconstriction is reproducible

27 of 39 studies reported significant effects in asthma; nine of 12 direct cold-versus-room-temperature comparisons produced more bronchoconstriction with cold air.

Typical protocol
### About −15 °C for ~4 minutes

The review proposes approximately four minutes at −15 °C with oral ventilation above 60% of maximal voluntary ventilation as a candidate standardized diagnostic challenge protocol.

Primary synthesis: Marain NF et al. [Exploring the role of cold air in airway hyperresponsiveness and asthma diagnostic testing: a systematic review and meta-analysis](https://pmc.ncbi.nlm.nih.gov/articles/PMC13169058/). European Respiratory Review, 2026. PROSPERO CRD42021290350.

Current prospective safety study

## CLARINET is almost a ready-made AIRCHILL airway-safety reference study.

[NCT07220928 / CLARINET](https://clinicaltrials.gov/study/NCT07220928) prospectively exposed 60 adults — healthy volunteers and people with mild-to-moderate asthma — to a standardized −15 °C eucapnic cold-air hyperventilation test. The study explicitly asks whether the protocol is safe and feasible and measures FEV1, cough/dyspnoea, small-airway function, sputum and blood inflammation, and epithelial-integrity markers. Recruitment and follow-up completed on 27 November 2024; as of the registry update, results have not been posted.

Why it matters
It moves beyond spirometry alone and directly measures airway integrity and inflammatory biology after cold-air inhalation.

What AIRCHILL should copy
Pre/post lung mechanics, symptom/adverse-event capture, epithelial-integrity biomarkers, local sputum markers and a room-temperature ventilation comparator.

What it cannot answer
It is short-duration spontaneous breathing in stable adults, not prolonged endotracheal ventilation in unconscious emergency patients.

Human cold-air challenge register

## All 39 studies included in the 2026 systematic review.

This table is a safety-oriented reconstruction of the review’s study and protocol tables. “NR” means symptoms/adverse events were not reported in the review table, not that none occurred.

StudyParticipants / conditionCold exposureDurationReported symptom / safety signal

Millar 1965n=15 · 5 healthy, 10 asthma−20 °C · normal breathing7 min2 patients: difficulty breathing

Strauss 1977n=8 · exercise-induced asthma−8 to −15 °C~3.4 min minimumNR

Deal 1980n=80 · healthy, hay fever, asthma−10 to −20 °C · 60–65 L/minNR35/40 patients: cough, dyspnoea, wheeze

O’Byrne 1982n=26 · 2 healthy, 24 asthma−18 °C · stepped flow to MVV3 min/levelBronchoconstriction endpoint

Higenbottam 1983n=14 · 7 healthy, 7 asthma−20 °C · 15×FEV11 minNR

Heaton 1983n=22 · 10 healthy, 12 asthmahealthy −22 to −25 °C; asthma −18 to −20 °C3 minNR

Aquilina 1983n=23 · 12 healthy, 11 asthma−10 °C · 70% MVV3 minDry mouth

Weiss 1983n=27 · asthma−14 to −21 °C · stepped ventilation4 min20% FEV1 fall used as threshold

Heaton 1984n=49 · 13 healthy, 36 asthmahealthy −22 to −25 °C; asthma −18 to −20 °C3 minAirway-conductance response

Zach 1984n=41 · 18 healthy, 23 asthma−10 to −20 °C · 75% MVV4 min1 child: discomfort with bronchoconstriction

Hodgson 1984n=18 · 9 healthy, 9 asthma−19.7±2.6 °C · 36 L/min10 minNR

Tal 1984n=23 · 10 healthy, 13 asthma−16 to −18 °C · 15×FEV14 min15% FEV1 fall threshold

Galdès-Sebaldt 1985n=33 · 12 healthy, 21 asthmamedian −16 °C (−2 to −24) · stepped ventilation3 min/levelNo symptoms

Malo 1986n=12 · asthma−20±5 °C · multiple ventilation methods3 min/level20% FEV1 fall threshold

Reisman 1987n=36 · 18 healthy, 18 asthma−15 °C (−12 to −20) · 25×FEV14–5 minNo symptoms

Tessier 1986n=20 · 7 healthy/former asthma, 13 asthma−20±5 °C · escalating flow3 min/level10% FEV1 fall threshold

Zach 1987n=17 · asthma−10 °C (−8 to −12) · 75% MVV4 minNR

Farley 1988n=14 · 7 healthy, 7 asthma−23.4 °C · 15/30/60 L/min3 min/levelNR

Filuk 1989n=140 · suspected asthma−17 to −20 °C · 30×FEV16 minSymptomatic bronchoconstriction in some

Lemire 1989n=11 · asthma−20 °C · stepped flow3 min/levelNo symptoms

Eliasson 1992n=40 · 20 healthy, 20 EIB−18 to −26 °C · 80% MVV5 minNR

Modl 1995n=28 · asthma−10 °C · 75% MVV4 min9% FEV1 fall threshold

de Benedictis 1995n=17 · asthma−15 °C (−12 to −20) · 25×FEV14–5 minNo symptoms

Sinclair 1995n=100 · asthma−5 to −10 °C · treadmill4–6 min + 2 min peakNR

Koskela 1995n=25 · 10 healthy, 15 asthma−17.2±0.6 °C · nasal tidal breathing10 min1 patient: severe cough

Julià-Serdà 1996n=22 · 7 healthy, 15 asthma−15 to −20 °C · MVV4 minNR

Koskela 1997n=313 · 26 healthy, 113 asthma, 174 symptomatic non-asthma−13.5 °C (−7.5 to −17) · 21–25×FEV13–4 minNo symptoms

Carlsen 1998n=58 · asthma/other chronic lung disease−20 °C · treadmill6 minNR

Nielsen 2000n=67 · 29 healthy, 38 asthma−15 °C · ~1 L/min/kg4 minNo symptoms

Koskela 2003n=47 · 10 healthy, 37 asthma−14.6 to −10.2 °C · 25×FEV14 minNR

Evans 2005n=22 · probable EIB−1 °C · 85% MVV6 minNR

Nielsen 2005n=40 · asthma, young children−15 °C · ~1 L/min/kg4 minNR

Sylvester 2007n=20 · asthma−15 °C · 24×FEV14 min15% FEV1 fall threshold

Sandsund 2007n=16 · 8 healthy, 8 asthma−15 °C · treadmill, 55–60% VO2max30 minExercise bronchoconstriction endpoint

Naumov 2015n=123 · mild/moderate persistent asthma−20 °C · 60% maximal minute ventilation3 min10% FEV1 fall threshold

Steinbacher 2017n=43 · asthma in remission−10 °C · 22.5×FEV14 minFEV1 response endpoint

Dreßler 2019n=67 · suspected EIB, children/adults2–4 °C · treadmill, 80–90% max HR6–8 min10% FEV1 fall threshold

Ahn 2022n=72 · paediatric asthma/other disease0 °C · 25×FEV14 minNo adverse events

Chavoshian 2024n=29 · 23 asthma, 6 healthy0/10/20 °C · cycle exercise10 minShortness of breath/chest tightness/dyspnoea increased in 22 asthma patients

Source for participant counts, temperatures, ventilation, duration and reported symptoms: Marain et al., European Respiratory Review 2026, Tables 1–2. The summed participant count of 1,778 is a MedicalCooling derived value from those table rows, not a number reported by the review authors. Individual studies can include repeated cold-air challenges.

Additional human evidence

## Several safety-relevant studies sit outside that 39-study diagnostic set.

Population scale
### Nicolai / von Mutius · 1993

Cold-air hyperventilation challenge was performed in 7,248 schoolchildren aged 9–11 in Bavaria as part of an asthma prevalence programme. The publication was diagnostic/epidemiological rather than a dedicated safety trial, so absence of a reported serious event must not be converted into proof that none occurred.

[PMID 8464856](https://pubmed.ncbi.nlm.nih.gov/8464856/)

Nasal physiology
### Fontanari · 1997 / Le Merre · 2003

Nasal cold dry air increased airway resistance in both normal and asthmatic participants in one controlled study; another study in nine healthy adults found a reflex reduction in tracheobronchial mucosal blood flow without a significant change in specific airway conductance.

[Fontanari et al.](https://pubmed.ncbi.nlm.nih.gov/9387948/) · [Le Merre et al.](https://pubmed.ncbi.nlm.nih.gov/15764066/)

Epithelial stress
### Cold exercise / prolonged exposure studies

Modern studies using cold exercise or approximately 50-minute cold exposure show small acute lung-function changes in healthy people but can increase Clara/club-cell protein CC16 and respiratory symptoms. These biomarker findings argue for measuring epithelial integrity in AIRCHILL rather than assuming histology alone answers the question.

Repeated challenge trials add exposure experience
Randomized asthma pharmacology trials repeatedly used cold dry air as the provocation method — including studies of cromolyn, beta-agonists, leukotriene/5-lipoxygenase inhibition, theophylline and other agents. These trials strengthen the evidence that supervised cold-air challenge is operationally feasible, but they were designed to measure bronchoprotection rather than long-term cold-air toxicity and should not be counted as independent proof of AIRCHILL safety.

AIRCHILL-specific evidence

## Our own data cover a gap the challenge literature does not.

Preclinical · prolonged
### −20 °C for six hours through an endotracheal tube

In the porcine programme, lung histology remained intact after six hours of cooled ventilation; perfusion did not materially change, CT showed no pulmonary oedema and the animals remained cardiorespiratorily stable. This is the most directly relevant evidence for prolonged lower-airway exposure, but it is animal evidence.

Human · short exposure
### 11 healthy volunteers

The project record documents 11 healthy volunteers tolerating cold air down to −20 °C for up to ten minutes. The peer-reviewed/public conference subset is smaller — two volunteers across three experiments — so the full 11-person cohort should be treated as project evidence until all original records are independently line-verified.

Clinical gap
### No emergency-patient AIRCHILL safety cohort yet

The external literature and animal work justify a staged clinical safety study. They do not justify the statement that AIRCHILL is already safe in intubated emergency patients.

See the [AIRCHILL Evidence page](https://www.medicalcooling.com/evidence/) for the BMBF final-report, histology, perfusion and thermometry evidence and the exact evidence-level wording used in the project claim register.

Cilia and mucociliary clearance

## Direct cold-air cilia data are still a genuine evidence gap.

Cold air can transiently slow ciliary activity, dry airway surfaces, increase mucus viscosity and reduce mucociliary transport. General airway-regeneration research shows that injured epithelium can rebuild ciliated cells from basal/secretory progenitors, but cold-specific human regeneration studies are sparse. Therefore a future AIRCHILL safety protocol should measure mucociliary function and secretion handling directly rather than infer them from general lung histology.

Acute functional gate
Airway resistance/compliance, peak and plateau pressures, gas exchange, secretion volume/viscosity, suction burden and bronchospasm.

Epithelial gate
CC16 and other epithelial-integrity markers, inflammatory markers, optional sputum/BAL sampling and clinically justified bronchoscopy in an early mechanistic cohort.

Mucociliary gate
Prespecified mucociliary-clearance or ciliary-function endpoint before claiming that prolonged cold-air ventilation leaves clearance unchanged.

Evidence-grade summary

## How good is the safety data today?

Safety questionCurrent evidenceAssessment

Can humans inhale very cold air for a few minutes under supervision?39-study review + additional large cohorts + repeated challenge trialsStrong / substantial

What is the main acute respiratory hazard?Consistent asthma/EIB literature: bronchoconstriction, cough, wheeze, dyspnoeaWell characterized

Is short exposure harmless to healthy airways?Mostly reassuring lung-function data; limited dedicated injury biomarkersModerate

Does cold air cause acute epithelial stress?CC16/inflammatory signals in exercise/prolonged cold exposure; CLARINET designed to investigate this prospectivelyLimited–moderate

Are cilia/mucociliary clearance preserved?Indirect physiology/regeneration evidence; little direct cold-air human evidenceLimited

Is prolonged −20 °C lower-airway ventilation safe?AIRCHILL porcine 6-hour histology/perfusion/CT dataPromising preclinical

Is AIRCHILL safe in intubated emergency patients?No direct prospective clinical AIRCHILL cohort yetNot yet established

Bottom line
The safety case is already considerably stronger than “cold air has barely been studied in humans.” There is decades of human exposure evidence and a 2026 systematic review that found no major adverse-event pattern. But the evidence is strongest for short diagnostic exposures and weakest exactly where AIRCHILL differs: prolonged, controlled lower-airway delivery in critically ill, intubated patients. That gap is narrow enough to design around — and important enough that the first clinical programme should be a dedicated performance-and-airway-safety study before any neurological-outcome claim.

[Use this in the clinical programme](https://www.medicalcooling.com/clinical-study-planner/)

Source policy

## What this register includes — and what it does not.

- Included: all 39 studies in the 2026 peer-reviewed systematic review of cold-air challenge, the large Bavarian paediatric population challenge, current CLARINET registry data, and selected mechanistic/epithelial studies with direct safety relevance.
- Not counted as independent safety proof: every pharmacology paper that merely used cold air as a provocation endpoint, occupational anecdotes, or general winter-exposure studies where the inspired temperature/dose cannot be isolated.
- No transfer without a label: spontaneous-breathing diagnostic tests do not establish the safety of endotracheal AIRCHILL delivery; porcine six-hour ventilation does not establish human emergency-patient safety.
- Living register: CLARINET results, new trials and any additional primary cold-air inhalation studies will be incorporated when verified.

Core sources: Marain NF et al., European Respiratory Review 2026 · ClinicalTrials.gov NCT07220928 (CLARINET) · Nicolai T, von Mutius E, Reitmeir P, Wjst M, Pneumologie 1993, PMID 8464856 · Hallstrand TS et al., ERS technical standard on indirect airway challenge testing, Eur Respir J 2018 · MedicalCooling AIRCHILL Evidence page and BMBF Go-Bio final report.

Temperature envelope · evidence + development assumption

## How cold can we currently defend?

There is no scientifically established single “safe minimum inspired temperature”. The airway dose depends on temperature, absolute humidity, minute ventilation/flow, duration, route and patient susceptibility. The coldest published controlled human inhalation exposure we identified is about −40 °C for 10 minutes in healthy exercising adults, but that experiment measured respiratory heat exchange rather than epithelial or ciliary injury. It therefore defines an observed exposure, not a safety threshold.

ExposurePopulation / routeWhat was observedHow AIRCHILL should use it

−40 °C · 10 min8 healthy adults, dry air, exercise at 80% predicted VO₂maxUpper-esophageal cooling showed that upper-airway conditioning capacity was exceeded and heat/water exchange extended deeper into the respiratory tract. No epithelial/cilia injury endpoint was measured.Exposure precedent only
Not evidence that −40 °C is safe for prolonged or intubated use.

−35 °C · 10 min6 healthy adults, rest + exercise up to ~75% VO₂maxNo complaints attributable to cold-air inhalation; oxygen uptake, respiratory rate and rectal temperature were not materially affected. Study was small and physiology-focused.Short human tolerance signal

−23 °C · ~2 h8 healthy nonsmokers, light intermittent workControlled crossover work found increased inflammatory cells in lower-airway lavage after cold exposure.Longer exposure warning
Duration and respiratory water loss matter even above −30 °C.

−15 °C · 50 min29 healthy adults, rest vs heavy exerciseSmall FEV₁ reductions and epithelial-stress signals; heavy exercise increased CC16, IL-8 and lower-airway symptoms.Dose interaction
High ventilation amplifies epithelial stress.

−20 °C · 6 hAIRCHILL porcine endotracheal ventilationProject evidence: intact lung histology, no relevant perfusion change or CT pulmonary oedema, cardiorespiratory stability under the tested conditions.Most route-relevant prolonged evidence
Preclinical, not human safety proof.

Provisional AIRCHILL development decision — ASSUMPTION, not a biological threshold
Use −20 °C as the provisional lowest setpoint for the first clinical-generation operating envelope. Start human dose escalation warmer (for example −10 °C → −15 °C → −20 °C) and expand only after prespecified airway, epithelial, mucociliary, pulmonary and haemodynamic gates are passed. Treat −25 °C as a new preclinical dose-finding level first. Treat −30 to −40 °C as research-only territory until prolonged route-specific safety data exist. This boundary is chosen because −20 °C has the strongest product-specific prolonged endotracheal evidence—not because −21 °C is known to be harmful.

Dose variable 1
### Temperature at the patient

Record device outlet, Y-piece and—during research—distal circuit/ETT temperature. Compressor setpoint alone is not a patient exposure.

Dose variable 2
### Water loss / humidity

Absolute humidity must be recorded and experimentally separated from temperature. Dryness itself can drive exercise-induced bronchoconstriction, so “cold” and “dry” cannot be treated as one variable.

Dose variable 3
### Ventilation × duration

Minute ventilation, peak inspiratory flow and cumulative exposure time determine how much heat and water the airway must exchange.

Key sources: Jaeger JJ et al. [Med Sci Sports Exerc. 1980;12:365–369](https://pubmed.ncbi.nlm.nih.gov/7453516/) (−40 °C); Hartung GH et al. [Aviat Space Environ Med. 1980;51:591–594](https://pubmed.ncbi.nlm.nih.gov/7417121/) (−35 °C); Eklund LM et al. [Eur J Appl Physiol. 2022;122:2533–2544](https://pubmed.ncbi.nlm.nih.gov/36053365/) (−15 °C, 50 min); AIRCHILL BMBF Go-Bio 031A530 project evidence for six-hour −20 °C porcine ventilation. Human extreme-cold exposure studies are not directly comparable to prolonged endotracheal delivery.

Trial watch · 23 August 2026

## No active direct cold-air inhalation safety trial was verified; one highly relevant study has completed.

Completed · results not posted
### CLARINET · NCT07220928

KU Leuven enrolled 60 healthy adults / adults with mild-to-moderate asthma. The protocol compares room-temperature EVH with a controlled −15 °C eucapnic cold-air challenge and measures FEV₁, symptoms, small-airway function, sputum/blood inflammation and epithelial-integrity markers. Completion: 27 Nov 2024. ClinicalTrials.gov currently shows no posted results.

[Open registry →](https://clinicaltrials.gov/study/NCT07220928)

Planned · registry not verified
### CLARINET2

The CLARINET registry explicitly states that its optimized protocol is intended to feed a subsequent prospective CLARINET2 diagnostic study. In the registry/public searches reviewed on 23 Aug 2026, we did not verify a separate public registration for CLARINET2. It therefore remains a planned study, not an ongoing registered trial in this database.

Data gap
### Direct AIRCHILL patient trial

No prospective AIRCHILL emergency-patient trial is yet registered. The external literature is used to define temperature, humidity, airway and cardiovascular safety gates—not to claim product safety.

Winter-sport evidence · repeated exposure

## What athlete data add to the AIRCHILL safety model.

Winter-sport studies are not direct AIRCHILL safety studies: athletes breathe spontaneously, often through the mouth, at very high ventilation over months or years. Their value is different—they reveal which airway injury mechanisms become important under repeated cold + dry + high-flow exposure.

Evidence familyMain findingWhat is new for AIRCHILL

Mäki-Heikkilä et al. 2020
systematic review/meta-analysis · 30 studiesSelf-reported physician-diagnosed asthma prevalence among competitive cross-country skiers was ~21% (95% CI 14–28%); asthma medication use ~23%. Bronchial-biopsy studies found airway inflammation even in some non-asthmatic skiers.Cumulative exposure matters. A short Phase-1 tolerance result cannot substitute for a duration/repetition safety programme.

2025 systematic review
50 studies · XC skiers + ice-hockey playersRepeated training/competition is associated with altered immune profiles and predominantly neutrophilic or mixed neutrophilic/eosinophilic airway inflammation rather than the classic eosinophilic allergic-asthma pattern.Inflammatory phenotype should be measured, not assumed. Add differential cell counts / sputum phenotype where feasible.

Frischhut et al. 2020
randomized crossover · −20 °C · winter-sport athletesWithout an HME, FVC and FEV₁ fell most shortly after exercise and respiratory symptoms were more frequent; HME use attenuated these changes.Heat/moisture recovery is a causal control variable. AIRCHILL should characterize absolute humidity and respiratory water loss alongside temperature.

Eklund et al. 2022 HME study
randomized crossover · −15 °C · 23 trained healthy participantsHME attenuated post-exercise FEV₁ decline and reduced plasma CC16 rise from +121% without HME to +27% with HME, with fewer symptoms.Strong mechanistic signal: epithelial stress can be reduced by returning heat and moisture even at the same environmental temperature.

Long-duration −15 °C study
ISRCTN1397775830 vs 90 min moderate exercise did not create major overall lung-function decrements, but CC16 increased after both and the 90-min exposure produced stronger leukocyte redistribution; atopic participants showed greater peripheral-airway/symptom responses.Susceptibility modifies dose response. Asthma/EIB/atopy should be explicit exclusion or stratification variables in early volunteer work.

Design consequence
The winter-sport evidence strengthens—not weakens—the current −20 °C development decision. It shows why a temperature ceiling alone is insufficient. The AIRCHILL clinical specification should ultimately constrain a delivered airway dose envelope: temperature, absolute humidity, minute ventilation/flow, exposure duration and repetition. If a warmer/more humid setting removes almost as much heat with materially less CC16, bronchoconstriction or mucociliary impairment, that setting is preferable even if the machine can technically produce colder gas.

Primary sources: [Mäki-Heikkilä et al., Sports Med 2020](https://pubmed.ncbi.nlm.nih.gov/32915429/) · [Systematic review 2025](https://pubmed.ncbi.nlm.nih.gov/40223161/) · [Frischhut et al. 2020](https://pubmed.ncbi.nlm.nih.gov/31755166/) · [Eklund/HME 2022](https://pubmed.ncbi.nlm.nih.gov/35391634/) · [duration study / ISRCTN13977758](https://pubmed.ncbi.nlm.nih.gov/35550109/).

Snowball search · additional airway studies

## Additional winter-sport studies that materially change the evidence map.

Backward/forward searching from the 2020 and 2025 systematic reviews identifies several useful studies beyond the initial seed list. The most informative additions are longitudinal inflammation data, challenge-test discordance, biomarker/remodeling work and a general-population counterexample.

StudyDesign / populationKey resultAIRCHILL relevance

Kennedy et al. 2016
PMID 26283581Longitudinal study, 18 elite female XC skiers across one training/racing yearSputum eosinophils and lymphocytes and cough burden increased from pre-season to winter. Change in total airway-cell count was strongly associated with yearly training hours.Repeated-dose evidence. Cumulative exposure and training volume can matter even when any single cold-air exposure is tolerated.

Sue-Chu et al. 2010
PMID 2046025758 elite XC skiers; methacholine, AMP, mannitol, EVH and field exercise challenges43% had airway hyperresponsiveness to at least one stimulus, but results differed markedly by test; many asymptomatic skiers were hyperresponsive.One airway test is insufficient. Early AIRCHILL safety should combine mechanics, symptoms and biological markers rather than use FEV1 alone.

Stenfors 2010
PMID 2070544246 elite XC skiersSelf-reported respiratory symptoms poorly predicted objective bronchial hyperresponsiveness.Symptoms cannot be the sole safety gate. Objective pulmonary endpoints are required even when subjects feel well.

Stang et al. 2018
PMID 29189668High-level skiers/swimmers with and without asthma vs non-athletesBHR was common in both asthmatic and non-asthmatic athletes; sputum IL-8 was higher in athletes, while conventional sputum inflammatory/epithelial cell counts were not clearly abnormal.Mechanisms may dissociate. Bronchial hyperresponsiveness, inflammation and epithelial injury should be measured separately.

Bougault et al. 2022
PMID 3492751041 winter-sport athletes, swimmers and controls; serum/sputum MMP-9/TIMP-1No simple group-level remodeling ratio predicted airway function. Seasonal changes occurred, and sputum MMP-9 related to methacholine responsiveness and CC16/SP-D balance.Do not overinterpret a single remodeling biomarker. Use a panel and longitudinal change rather than one cutoff.

Kotaniemi et al. 2003
PMID 12862178Large general-population survey; 1,497 recreational XC skiersRegular recreational skiing was not associated with significantly increased asthma or respiratory-symptom risk.Important counterexample. Cold climate / recreational exposure alone is not enough to recreate the elite-athlete phenotype; very high ventilation, intensity and cumulative dose are likely important modifiers.

Lumme et al. 2003
PMID 1288246088 elite ice-hockey players + controls22% total asthma; 24% BHR; induced sputum showed markedly higher neutrophils and eosinophils than controls.Pollutant confounding. Ice-rink air can combine cold exposure with combustion/particulate pollutants; this evidence cannot be assigned to cold alone.

Updated causal interpretation
The snowball corpus makes a simple “cold air damages airways” narrative too crude. The better-supported model is that high ventilation of inadequately warmed/humidified air, repeated for long periods, with sport-specific pollutant and host-susceptibility modifiers can produce bronchial hyperresponsiveness, inflammatory phenotypes and remodeling. Recreational cold exposure does not consistently reproduce this risk. This distinction is favorable for AIRCHILL risk analysis because the device can tightly control flow, duration, gas purity, oxygen concentration and potentially humidity—but those variables must actually be measured and bounded.

Sources: [Kennedy 2016](https://pubmed.ncbi.nlm.nih.gov/26283581/) · [Sue-Chu 2010](https://pubmed.ncbi.nlm.nih.gov/20460257/) · [Stenfors 2010](https://pubmed.ncbi.nlm.nih.gov/20705442/) · [Stang 2018](https://pubmed.ncbi.nlm.nih.gov/29189668/) · [Bougault 2022](https://pubmed.ncbi.nlm.nih.gov/34927510/) · [Kotaniemi 2003](https://pubmed.ncbi.nlm.nih.gov/12862178/) · [Lumme 2003](https://pubmed.ncbi.nlm.nih.gov/12882460/).

Comparator register · endurance sport airways

## Winter sport is high risk—but not uniquely so.

The best cross-sport evidence indicates that lower-airway dysfunction tracks with endurance ventilation load plus the inhaled environment. This makes cycling, swimming, triathlon, rowing and running useful comparator groups for separating cold/dry-air effects from high-volume breathing itself.

Sport / populationAsthma / AHR / lower-airway dysfunctionExposure patternInterpretation for AIRCHILL

All athletes · 2022 meta-analysis
64 studies · 37,643 athletesLower-airway dysfunction 21.8% overall; elite endurance 25.1%Mixed sports / methodsHigh training ventilation alone is a major background risk. Cold-air effects must be judged against this baseline.

Winter-based sports29.5% lower-airway dysfunction in 2022 meta-analysisHigh ventilation + cold/dry airSupports cold/dry air as an important modifier, but not the only causal exposure.

Aquatic sports39.9% lower-airway dysfunction in 2022 meta-analysisHigh ventilation + chloramines / humid pool environmentKey comparator: airway dysfunction can be at least as common without cold air when ventilation and irritants are high.

Olympic cycling~17% asthma/AHR in Olympic surveillance summariesVery high ventilation + PM/NOx/ozone/pollen, usually not severe coldUseful comparator for ventilation + pollution without a dominant cold-air exposure.

Professional cycling team
Medelli et al. 2006 · n=2552% showed symptoms associated with methacholine bronchial responsivenessElite road cyclingSmall single-team study; BHR is not asthma. Still shows that extreme endurance training can produce striking objective airway reactivity in a non-winter sport.

Grand Tour cyclists
Allen et al. 2021 · n=9Not an asthma-prevalence study; 7/9 symptomaticTour de France / Vuelta, three-week competitionMean FEV₁ fell ~0.27 L / 5.7% from pre-race to mid/late race; 8/9 had >200 mL FEV₁ decline at least once. Demonstrates cumulative respiratory stress during sustained elite cycling.

Olympic triathlon~25% asthma/AHR in Olympic surveillance summariesSwimming + cycling + runningOne of the highest Olympic rates; supports cumulative environmental + ventilation burden.

Olympic swimming~17% asthma/AHR in Olympic surveillance; some swimmer cohorts report much higher BHRHigh ventilation + chloramine exposureStrong non-cold comparator for epithelial injury / airway hyperresponsiveness.

Cross-country skiing~17% Olympic asthma/AHR surveillance; broader ski-specific reviews report ~21–27% physician-diagnosed asthma and higher combined EIB/BHRHigh ventilation + cold/dry airCold-air-specific comparator with substantial repeated-exposure evidence.

Speed skating~15% asthma/AHR in Olympic surveillanceCold rink air + high ventilation; possible indoor pollutantsIntermediate cold-air comparator; less prolonged outdoor exposure than XC skiing.

Ski jumping / alpineMuch lower Olympic surveillance rates (~2–4% range in published summaries)Cold environment but far lower sustained ventilationNatural experiment: similar cold weather with much less hyperpnoea produces far less asthma/AHR. Strongly supports ventilation dose as a central causal modifier.

Cross-sport causal lesson
The strongest comparator pattern is not “winter sport versus summer sport”. It is sustained high ventilation + an airway-stressing environment versus lower ventilation. Cross-country skiing adds cold/dry air; swimming adds chloramines; road cycling adds particulate/ozone/allergen exposure. Alpine skiing and ski jumping are especially informative because athletes share cold conditions but not the same prolonged ventilation load, and their asthma/AHR rates are much lower in Olympic surveillance. For AIRCHILL risk analysis, this supports treating minute ventilation, humidity, duration and gas purity as primary exposure variables alongside temperature.

Sources: [Price et al. 2022 systematic review/meta-analysis](https://pubmed.ncbi.nlm.nih.gov/34872908/) · [Fitch 2012 Olympic asthma/AHR overview](https://pubmed.ncbi.nlm.nih.gov/22228581/) · [Medelli et al. 2006 professional cyclists](https://pubmed.ncbi.nlm.nih.gov/16823362/) · [Allen et al. 2021 Grand Tour](https://pubmed.ncbi.nlm.nih.gov/33420604/) · [Kippelen/Anderson critical review](https://pmc.ncbi.nlm.nih.gov/articles/PMC3371227/).