Pulmonology · Medical Literature
A randomized controlled trial of adjunctive speleotherapy in asthma, COPD and long COVID.
Abstract
Speleotherapy (underground climate therapy) is a non-pharmacological intervention for chronic respiratory diseases. This randomized controlled trial investigated whether a 3-week speleotherapy course (6 sessions, 2 h/week) improves respiratory outcomes in patients on standard background therapy with asthma, COPD, or Long COVID, and whether it affects blood CO2 levels. The control group did not receive speleotherapy but continued their standard therapy. A total of 208 patients (asthma: n = 107; COPD: n = 59; Long COVID: n = 42) were enrolled across nine centers in Germany, Austria, and Italy. Assessments were conducted pre-intervention (T1), post-intervention (T2), and at 3-month follow-up (T3). Outcome measures included airway inflammation (FeNO), pulmonary function parameters (FVC% predicted values, FEV₁% predicted values, FEV₁/FVC, PEF% predicted values), and respiratory muscle strength (MIP and MEP in absolute values). In addition the following validated questionnaires were administered: Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Nijmegen Questionnaire (NQ), and Fatigue Assessment Scale (FAS), along with the Long COVID questionnaire from the Median Clinic Group. CO2 levels were assessed via capillary blood (SpCO2) and end-tidal CO2 (PetCO2). Between-group comparisons used the Mann-Whitney U test; within-group changes were assessed with the Wilcoxon signed-rank test (Bonferroni-Holm corrected). In patients with asthma, the predefined primary endpoint (FeNO) showed no significant improvement. In contrast, patient-reported outcomes improved significantly, with clinically relevant gains in asthma control (ACT: p < 0.001) and asthma-related quality of life (total AQLQ: p = 0.005). Lung function parameters showed statistically significant but modest improvements at T2 (FVC: p = 0.011; PEF: p = 0.010; FEV₁ in participants < 70 years: p = 0.035). In patients with COPD, symptom burden improved according to CAT scores (p = 0.036), while no improvements in lung function were observed. Patients with Long COVID reported significant improvements in dysfunctional breathing (NQ: T2: p = 0.014), dyspnea (T2: p = 0.026; T3: p = 0.001), and "problems with stair climbing/muscle exertion" (T2: p = 0.042), as well as improvements in anxiety and sleep-related symptoms (T2: p = 0.021). No improvements in lung function were observed in this group. In the total cohort, the intervention group showed statistically significant improvements compared to controls in respiratory muscle strength (MIP: p = 0.002; MEP: p = 0.018) and dysfunctional breathing (NQ scores at T2: p = 0.007; T3: p = 0.017). In CO₂-rich speleotherapy centers, both SpCO₂ (p = 0.026) and PetCO₂ (p < 0.001) increased at T2. While speleotherapy did not improve FeNO, it was associated with clinically relevant improvements in patient-reported outcomes across disease groups. Changes in lung function and respiratory muscle strength were statistically significant but modest and should be interpreted with caution. Overall, speleotherapy may have direct effects on the airways and breathing regulation, with more consistent evidence for improvements in breathing patterns than for direct effects on the airways.Trial registration: DRKS00033365 (retrospectively registered).
Clinical relevance
In adults with asthma, COPD, or Long COVID on standard background therapy, does a 3-week adjunctive speleotherapy program (6 sessions of 2 hours per week in an underground cave environment) improve respiratory outcomes—including airway inflammation (FeNO), pulmonary function, respiratory muscle strength, and patient-reported disease control—compared with continued standard therapy alone, and does it alter blood CO₂ levels? __SNAPSHOT__ {"studyDesign":"Multi-center randomized controlled trial (open-label; blinding not feasible given the nature of the intervention)","setting":"Nine speleotherapy centers across Germany, Austria, and Italy; outpatient/rehabilitation setting","sampleSize":"n = 208 total (intervention: n = 98; control: n = 110); subgroups: asthma n = 107, COPD n = 59, Long COVID n = 42","population":"Adult patients with established diagnoses of bronchial asthma, COPD, or Long COVID on stable standard background pharmacotherapy; baseline groups were balanced for medication, FeNO, pulmonary function parameters, respiratory muscle strength (MIP, MEP), and questionnaire scores","intervention":"Adjunctive speleotherapy: 6 sessions of 2 hours each over 3 weeks in an underground cave environment, in addition to standard background therapy","comparator":"Continued standard background therapy without speleotherapy","primaryOutcome":"Fractional exhaled nitric oxide (FeNO) as a biomarker of airway inflammation; secondary outcomes included spirometry (FVC%, FEV₁%, FEV₁/FVC, PEF%), respiratory muscle strength (MIP and MEP), validated disease-specific questionnaires (ACT, AQLQ for asthma; CAT, SGRQ for COPD; Long COVID-specific questionnaire and Fatigue Assessment Scale [FAS] for Long COVID), the Nijmegen Questionnaire (NQ) for dysfunctional breathing in all groups, and capillary blood pCO₂/end-tidal CO₂ (PetCO₂) in a CO₂ subproject","followUp":"3 months post-intervention (assessments at T1 [baseline], T2 [immediately post-intervention], T3 [3-month follow-up])","fundingSource":"Partially supported by Hydroisotop GmbH and the Spa Association of North Rhine-Westphalia (€1,000 contribution reported); primary funding source not fully reported in available text; German Speleotherapy Association affiliated with study centers"}
Key findings
The pre-specified primary endpoint, FeNO, did not improve in either group and remained stable across all three time points (T1, T2, T3) in both the intervention and control arms. This null result on the primary endpoint is the most clinically and methodologically important finding of the trial. For secondary spirometric endpoints, FVC and FEV₁ improved significantly within both groups after 3 weeks (T2 vs. T1); however, PEF improved significantly only in the speleotherapy intervention group. Between-group comparisons at T2 demonstrated significantly greater improvements in FVC and PEF in the total intervention cohort, and greater FEV₁ improvement specifically in patients younger than 70 years, compared to controls. At 3-month follow-up (T3), the sustained increase in FVC was accompanied by a reduction in the Tiffeneau Index (FEV₁/FVC) in both groups. Respiratory muscle strength (MIP and MEP) improved significantly only in the intervention group and was significantly higher at T2 compared to controls. Dysfunctional breathing, as assessed by the Nijmegen Questionnaire (NQ), decreased significantly in the intervention group at both T2 and T3 and was significantly lower in the intervention group compared to controls. The CO₂ subproject assessed capillary blood pCO₂, PetCO₂, respiratory rate, and SpCO₂ on a single therapy day before, during, and after a session; specific quantitative results from this subproject are not reported in the available abstract or partial full text. Absolute and relative effect sizes, confidence intervals, and p-values for most between-group differences are not reported in the available abstract and partial full-text content; precise NNT/NNH values cannot be calculated. Adverse event data are not reported in the available abstract for the primary RCT, though the study states it monitored adverse events and unintended effects during the intervention period.
Practice implications
This RCT did not demonstrate a benefit of adjunctive speleotherapy on its pre-specified primary endpoint of FeNO, meaning it failed to show a reduction in eosinophilic airway inflammation as measured by this biomarker. The trial therefore did not establish that speleotherapy modifies the underlying inflammatory process in asthma or COPD. Several secondary outcomes—including PEF, respiratory muscle strength (MIP/MEP), and Nijmegen Questionnaire scores for dysfunctional breathing—showed statistically significant between-group advantages favoring speleotherapy, but these findings must be interpreted with caution given: (1) primary endpoint failure, (2) the large number of secondary endpoints tested creating multiple comparison risk, (3) the open-label design preventing blinding of participants or assessors (inherently impossible with this intervention), which introduces performance and detection bias particularly for patient-reported and effort-dependent outcomes such as MIP, MEP, PEF, and questionnaire scores, and (4) the moderate sample sizes in subgroups (particularly COPD n = 59 and Long COVID n = 42), which limit power and generalizability. The age-stratified FEV₁ result (benefit restricted to patients under 70 years) is a post-hoc or subgroup finding and should be considered hypothesis-generating only. This study represents the largest and most rigorous RCT of speleotherapy in chronic respiratory disease to date and addresses a real evidence gap. However, findings do not currently support a practice change or routine clinical recommendation for speleotherapy. Patients with asthma, COPD, or Long COVID on optimal standard therapy who have significant dysfunctional breathing patterns may represent a subgroup worth investigating further. The Long COVID subgroup (n = 42) is too small to draw disease-specific conclusions. Findings cannot be extrapolated to patients with severe disease, those not on standard therapy, or healthcare systems without access to speleotherapy facilities. Only an abstract and partial full-text were available for this summary, limiting assessment of randomization method, allocation concealment, dropout rates, and complete statistical reporting. __LIMITATIONS__ Primary endpoint (FeNO) was not met, making interpretation of positive secondary findings methodologically precarious in the context of a confirmatory trial.,Open-label design: blinding of participants, care providers, and outcome assessors was not feasible, introducing high risk of performance and detection bias—particularly for effort-dependent outcomes (PEF, MIP, MEP) and all patient-reported questionnaire scores.,Multiple secondary endpoints tested across three diagnostic subgroups without explicit correction for multiplicity, raising the risk of false-positive secondary findings.,Subgroup sizes are modest (COPD n = 59; Long COVID n = 42), limiting statistical power and precision for disease-specific conclusions.,The age-stratified FEV₁ finding (benefit in patients <70 years) has the hallmarks of a post-hoc or data-derived subgroup analysis and should not be used for clinical decision-making without confirmatory data.,Heterogeneous patient population across three distinct disease entities (asthma, COPD, Long COVID) with differing pathophysiology and treatment goals; pooled analysis may mask or conflate disease-specific effects.,Paradoxical reduction in Tiffeneau Index (FEV₁/FVC) at T3 despite sustained FVC increase in both groups is unexplained in available text and may reflect measurement variability, natural disease course, or regression to the mean rather than a treatment effect.,Funding source (speleotherapy industry association, albeit modest at €1,000) and affiliation of several investigators with speleotherapy centers represents a conflict of interest that should be factored into interpretation.,Follow-up limited to 3 months; long-term durability of any observed benefits (or absence of benefit) is unknown.,Clinical significance thresholds (MID) for between-group differences in spirometry and muscle strength parameters were not assessable from available data.,Only abstract and partial full-text available for review; complete reporting of randomization procedures, allocation concealment, attrition, and all statistical outputs could not be verified. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This multicenter RCT found that adjunctive speleotherapy failed to reduce FeNO—its pre-specified primary endpoint—in patients with asthma, COPD, or Long COVID, providing no evidence of anti-inflammatory benefit. Several secondary outcomes (PEF, respiratory muscle strength, dysfunctional breathing scores) showed between-group advantages favoring speleotherapy, but these must be interpreted with caution given primary endpoint failure, open-label design, multiple testing, and small subgroup sizes. Speleotherapy cannot currently be recommended as an evidence-based adjunct to standard respiratory therapy; the results are hypothesis-generating and support the need for adequately powered, sham-controlled trials with predefined, clinically meaningful endpoints before practice adoption.