ABSTRACT
Objective
To evaluate whether Provox Life Heat and Moisture Exchangers (HMEs) and attachments enable HME‐naïve laryngectomized patients to establish a 24‐h HME routine, and whether the resulting effect on pulmonary symptoms is sustained over 9 months, compared with standard care.
Methods
In this prospective, randomized controlled trial, 79 HME‐naïve patients post‐total laryngectomy at two Brazilian centers were randomized to the Provox Life group (n = 41) or a control group without HMEs (n = 38). Data were collected at baseline and at 3, 6, and 9 months. The primary endpoint was the Cough Symptoms (COUS) domain of the validated Cough and Sputum Assessment Questionnaire (CASA‐Q). Secondary endpoints included other CASA‐Q domains, forced expectorations, involuntary coughs, sleep quality (JSEQ), quality of life (EQ‐5D‐5L), shortness of breath, skin integrity, pulmonary complications, and patient satisfaction.
Results
HME adherence was near‐continuous (mean 23.3–23.9 h/day). All four CASA‐Q domains (COUS, COUI, SPUS, SPUI) improved significantly from baseline in the Provox Life group (all p ≤ 0.001 at 9 months), with changes exceeding published minimal clinically important differences; controls remained stable except for transient sputum‐domain gains at T2. At 9 months, forced expectorations were significantly lower in the Provox Life group versus controls (3.3 ± 2.2 vs. 6.6 ± 6.1 per 24 h; p = 0.023). Sleep quality (JSEQ) improved significantly with Provox Life (p = 0.013), but not in controls. The EQ‐5D‐5L index improved at 3 and 6 months, pulmonary complications were descriptively fewer, and 89.7% rated their experience “very good”. Skin irritation was low and comparable between groups. No device‐related serious adverse events occurred.
Conclusion
In HME‐naïve patients after total laryngectomy, Provox Life enables near‐continuous HME use and is associated with clinically meaningful improvements in pulmonary symptom burden, sputum management, and sleep quality. Skin tolerability is comparable to standard care.
Level of Evidence
1b
Trial Registration: ClinicalTrials.gov identifier: NCT06084611.
Keywords: cough, heat and moisture exchanger, HME, laryngectomy, Provox Life, pulmonary rehabilitation, randomized controlled trial, tracheal humidification
1. Introduction
Total laryngectomy permanently alters respiratory physiology by bypassing the upper airway, eliminating the humidification, warming, and filtering functions of the nose and mouth. Cold, dry air entering the tracheobronchial tree directly leads to increased mucus production, excessive coughing, forced expectorations, tracheal irritation, disrupted sleep, and higher rates of pulmonary complications including pneumonia and tracheobronchitis [1, 2, 3]. Pulmonary rehabilitation with heat and moisture exchangers (HMEs) is considered standard of care for laryngectomized patients in many countries [4].
That HME use benefits patients who have never used one is not a new observation. Ackerstaff et al. reported reductions in involuntary coughing and forced expectoration within weeks of first HME use as early as 1993 [4]. Bien et al., in a randomized study of HME‐naïve laryngectomees, found significant reductions in coughing and expectoration within 3 months [5], and Parrilla et al. observed a fall in forced expectorations from 6.3 to 1.9 per day at 12 weeks, most of it established within the first 2 weeks [6].
Two problems have nonetheless persisted. The first is adherence: with legacy devices only about half of HME‐naïve patients achieved full day‐and‐night use at 3 months, and reported adherence has ranged from 35% to 70%, largely because of breathing resistance during activity and problems with peristomal attachment [5, 6]. The second is durability: previous HME‐naïve studies followed patients for only 6–12 weeks, so it is unknown whether early gains persist over time.
HMEs are passive devices attached over the tracheostoma that capture exhaled heat and moisture and return them during inhalation. Consistent 24‐h use has been associated with significant reductions in coughing, forced expectorations, and mucus burden, as well as improved sleep and quality of life [1, 2]. Because the earlier HME‐naïve studies relied largely on event counts, the present trial was designed around validated patient‐reported instruments with established minimal clinically important differences, allowing symptom burden to be interpreted against thresholds of clinical relevance rather than statistical significance alone [7, 8, 9].
Provox Life (Atos Medical AB, Malmö, Sweden) is a third‐generation HME range designed to address these barriers: it comprises five situation‐specific HMEs (for rest, activity, sleep, protection, and physical exertion) and a range of adhesives for different skin types and stoma shapes, and its HME diameter was increased from 22 to 23 mm to improve humidification while lowering breathing resistance. Prior studies have demonstrated significant pulmonary improvements when patients transitioned to Provox Life from legacy devices [1, 2], but the efficacy of initiating this range in HME‐naïve patients had not been evaluated in a controlled, prospective design.
This prospective randomized controlled trial therefore tested not whether HMEs work, but whether a range of situation‐specific devices with lower resistance and individualized attachment removes the two barriers above. Two aims were pre‐specified: to determine whether HME‐naïve patients can establish and maintain a genuine 24‐h routine, and to determine whether the resulting effect on pulmonary symptoms is sustained beyond the early adaptation window, over a 9‐month follow‐up, against a parallel standard‐care group followed over the same calendar period. The primary endpoint was the change in cough symptoms over the 9‐month follow‐up.
2. Materials and Methods
2.1. Study Design
This was a prospective, open‐label, randomized controlled trial at two Brazilian centers (Instituto de Câncer Dr. Arnaldo [ICAVC] and Santa Casa de São Paulo). The 9‐month follow‐up was fixed in the clinical investigation plan, with no shorter assessment window; a parallel non‐HME group was followed over the same calendar period so that seasonal variation could be visualized rather than mistaken for treatment effect. This post‐market study of CE‐marked devices complied with ISO 14155:2020, the Declaration of Helsinki, and Good Clinical Practice, with ethics approval from the ICAVC Research Ethics Committee (CAAE 75671523.3.1001.5471) and registration at ClinicalTrials.gov (NCT06084611). Written informed consent was obtained from all participants.
2.2. Participants and Recruitment
Participants were both recruited consecutively after surgery and identified from the population of laryngectomized patients under long‐term outpatient follow‐up at the participating centers, screened at a single time point during the enrollment window (26 March to 29 November 2024; last follow‐up 27 August 2025). The cohort therefore spans the full post‐laryngectomy spectrum, from patients recently discharged from adjuvant treatment to patients breathing through an open tracheostoma for over two decades (3–281 months since surgery). Eligible participants were adults (≥ 18 years) who had undergone total laryngectomy at least 3 months prior to enrollment, completed postoperative radiotherapy ≥ 6 weeks before enrollment, and had not used HMEs in the preceding 90 days (a washout considered sufficient to exclude residual effects of prior exposure on baseline assessments). Exclusion criteria included active or metastatic disease affecting pulmonary health, ongoing pulmonary infection, medical contraindication to HME use, low tidal volume, insufficient capacity to operate devices, or inability to provide informed consent.
2.3. Randomization and Treatment Allocation
Participants were randomized 1:1 via electronic case report form (Castor EDC), stratified by age, smoking history, chronic pulmonary disease, and voice prosthesis use, with computer‐generated allocation and complete concealment. The Provox Life group received the full device range—five HME variants (Home, Go, Energy, Protect, Night), four adhesive types, LaryTubes in multiple configurations, and associated accessories—with a goal of 24/7 use for 9 months. Patients allocated to standard care continued usual stoma care and were neither given nor instructed to use any HME; no humidification regimen (external humidifier, steam inhalation, or scheduled saline instillation) was prescribed and no HME‐related counseling was given. Usual care consisted of passive stoma covering according to individual habit, with no covers supplied by the study; the covers used were recorded at every visit in both arms. Blinding was not feasible given the external, visible nature of the devices.
2.4. Outcome Measures and Data Collection
Data were collected at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). Questionnaires were patient‐reported and completed at the study visit; investigators recorded adverse events, device deficiencies, and clinical findings; a device‐use diary and a 3‐day tally sheet were completed at home between visits. All analyses were performed by the sponsor.
The primary endpoint was change in the Cough Symptoms (COUS) domain of the CASA‐Q, a validated instrument comprising COUS, Cough Impact (COUI), Sputum Symptoms (SPUS), and Sputum Impact (SPUI), each scored 0–100 (higher = fewer symptoms) [7, 8]. Published minimal clinically important differences (MCIDs) are 10.6, 10.1, 9.5, and 7.8 points [9]; these served for interpretation only and formed no part of the statistical hypothesis.
Secondary endpoints were the remaining CASA‐Q domains; forced expectorations and involuntary coughs per 24 h from a 3‐day tally sheet (T1–T3 only, since the clinical investigation plan did not collect a baseline tally sheet); sleep (Jenkins Sleep Evaluation Questionnaire, JSEQ; lower = better) [10]; quality of life (EQ‐5D‐5L index and EQ VAS) [11]; shortness of breath [4]; voice handicap (VHI‐10, voice‐prosthesis users only) [12]; HME adherence and device‐use pattern; and, on study‐specific patient‐reported instruments, peristomal skin integrity, stomal management, pulmonary complications and patient experience (comparative questions in both arms; satisfaction questionnaire in the Provox Life arm only). All instruments, items and scoring are described in Appendix S1. Pulmonary complications (mucus plugging, tracheitis, tracheobronchitis, pneumonia and other pulmonary problems) were patient‐reported at each visit for the preceding 3 months and entered by the investigator, who cross‐checked them against the medical record and adverse‐event forms where records were available. No pre‐specified diagnostic criteria were applied: episodes reflect a diagnosis made in routine care rather than protocol‐defined case definitions. Pneumonia was managed according to institutional protocol, with home antibiotic treatment for mild to moderate cases and hospitalization when signs of severity were present. Episodes managed at other institutions, and hospitalizations of patients who died before the subsequent visit, may not have been captured.
2.5. Statistical Analysis
Sample size required 34 participants per group (80% power, two‐sided α = 0.05, COUS domain); with a 20% dropout allowance, 79 were enrolled. Normality was assessed by Shapiro–Wilk. Between‐group comparisons used the independent t‐test, Wilcoxon‐Mann–Whitney, or chi‐square; within‐group changes used ANOVA, Friedman with Wilcoxon signed‐rank post hoc tests (Bonferroni correction), or Cochran's Q for binary outcomes. Analysis was intention‐to‐treat; all tests were two‐tailed (α = 0.05).
No changes to the trial protocol or eligibility criteria were made after the trial commenced. No interim analyses or stopping rules were applied. The random allocation sequence was computer‐generated by the Castor EDC system; the principal investigator and enrolling personnel had no access to the allocation sequence. Analysis followed the intention‐to‐treat principle; missing data were not imputed, and outcomes were analyzed for the available cases at each timepoint.
3. Results
3.1. Participants
Of the 81 patients screened, 79 were enrolled (Provox Life n = 41; control n = 38); the two not enrolled did not meet the selection criteria, and none declined participation. During follow‐up, 8 participants died from causes unrelated to the device (cancer recurrence, pneumonia, or ruptured carotid artery) and 5 withdrew voluntarily (2 control patients independently initiated HME use, 2 were lost to follow‐up, and 1 Provox Life patient discontinued due to device discomfort). At T3, 39 Provox Life and 27 control patients completed the final assessment.
Baseline characteristics were balanced following stratified randomization, with no significant between‐group differences in age (66.3 vs. 66.7 years), smoking history, chronic pulmonary disease, or voice prosthesis use (Table 1). Most patients had advanced tumor stage (T4: 75.9%), laryngeal primary site (91.1%), and no distant metastases. Time since laryngectomy was highly heterogeneous (median 30 months, range 2–277): 19 participants (24.4%) were within 12 months of surgery, and 17 (21.8%) were five or more years beyond it, including 8 (10.3%) beyond a decade. Exposure was longer in the control arm (median 33 vs. 27 months), with 12 of 38 controls (31.6%) beyond 5 years versus 5 of 40 (12.5%) in the Provox Life arm.
TABLE 1.
Baseline demographic and clinical characteristics of the study population, by treatment arm.
| Characteristic | Provox Life (N = 41) | Control (N = 38) |
|---|---|---|
| Mean age (years) [median; range] | 66.3 [66; 43–86] | 66.7 [66; 45–90] |
| Male, N (%) | 33 (80.5%) | 31 (81.6%) |
| History of smoking, N (%) | 37 (90.2%) | 36 (94.7%) |
| Chronic pulmonary disease, N (%) | 2 (4.9%) | 1 (2.6%) |
| Voice prosthesis use, N (%) | 9 (22.0%) | 9 (23.7%) |
| Primary tumor site: Larynx, N (%) | ~91% | ~91% |
| T4 tumor stage, N (%) | ~76% | ~76% |
| Time since laryngectomy (months), median [IQR] | ~27 [12–46] | 33 [12–77] |
| Flat or flat/irregular stoma shape, N (%) | ~57% | ~57% |
Stoma care in the control arm remained passive throughout: a cloth bib was the commonest cover and no foam bib or foam filter was used at any timepoint in either arm; self‐initiated humidifier or saline use was infrequent and comparable between arms (Appendix S1).
3.2. Adherence and Pattern of Device Use
Adherence was near‐continuous from the first follow‐up: mean daily use was 23.5 ± 1.8 h (T1), 23.3 ± 3.7 h (T2) and 23.9 ± 0.7 h (T3), median 24 h throughout, with nighttime use reported by 97.5%–100% of patients; showering and transient skin irritation were the commonest reasons for partial non‐use. Patients did not simply alternate one daytime with one nighttime device: they used a mean of 2.8 (T1) to 3.0 (T3) HMEs per 24 h and chose the variant by situation—at T3, Home every day in 33 of 39 patients and predominantly when relaxing at home (37/39), Go every day in 27 of 39 and predominantly when out of the house, during physical activity, in crowded places and at hospital visits (28–36/39), and Night every night in 36 of 39 and during sleep in 38 of 39, while Protect was reserved for hospital, dusty or crowded environments and Energy used only during intense exercise, by one patient. Adhesive use was daily in 30–33 patients, most often the Sensitive type, while 6–7 used a LaryTube alone. The typical participant therefore wore an HME for essentially the whole 24‐h cycle and passed through at least three devices in doing so.
3.3. Primary Endpoint: Cough Symptoms (COUS)
COUS scores in the Provox Life group increased from 60.4 ± 20.6 at T0 to 68.3 ± 19.4 at T1, 76.5 ± 15.3 at T2 and 73.7 ± 17.6 at T3, reflecting progressive symptom reduction. Within‐group improvement was statistically significant from T0 to T2 (p = 0.0003) and T0 to T3 (p = 0.001), with changes exceeding the published MCID of 10.6 points. COUS scores in the control group remained stable throughout (T0: 62.5; T3: 70.4), with no significant within‐group changes at any timepoint (Table 2).
TABLE 2.
Cough and Sputum Assessment Questionnaire (CASA‐Q) domain scores at each study visit, by treatment arm, with within‐group comparisons against baseline.
| Domain | Group | T0 (Mean ± SD) | T1 (Mean ± SD) | T2 (Mean ± SD) | T3 (Mean ± SD) | p‐value (vs. T0) |
|---|---|---|---|---|---|---|
| Cough symptoms (COUS) | Control | 62.5 ± 26.3 | 60.6 ± 26.5 | 70.4 ± 23.3 | 70.4 ± 20.0 | T1: 0.876 |
| T2: 0.774 | ||||||
| T3: > 0.999 | ||||||
| Provox Life | 60.4 ± 20.6 | 68.3 ± 19.4 | 76.5 ± 15.3 | 73.7 ± 17.6 | T1: 0.095 | |
| T2: 0.0003* | ||||||
| T3: 0.001* | ||||||
| Cough impact (COUI) | Control | 72.4 ± 23.6 | 74.8 ± 28.1 | 79.1 ± 22.9 | 80.7 ± 25.1 | T1: 0.657 |
| T2: 0.832 | ||||||
| T3: 0.675 | ||||||
| Provox Life | 70.8 ± 22.2 | 86.4 ± 14.2 | 91.4 ± 9.6 | 89.9 ± 14.5 | T1: 0.0003* | |
| T2: 0.0003* | ||||||
| T3: 0.0003* | ||||||
| Sputum symptoms (SPUS) | Control | 48.1 ± 22.8 | 51.9 ± 21.9 | 59.7 ± 21.6 | 61.1 ± 23.2 | T1: 0.892 |
| T2: 0.014* | ||||||
| T3: 0.056 | ||||||
| Provox Life | 53.9 ± 23.7 | 70.4 ± 12.8 | 72.9 ± 17.0 | 74.4 ± 14.6 | T1: 0.0003* | |
| T2: 0.002* | ||||||
| T3: 0.0003* | ||||||
| Sputum impact (SPUI) | Control | 60.2 ± 25.9 | 68.2 ± 28.1 | 73.0 ± 25.2 | 72.1 ± 27.3 | T1: 0.066 |
| T2: 0.012* | ||||||
| T3: 0.083 | ||||||
| Provox Life | 64.0 ± 28.4 | 82.3 ± 16.4 | 87.6 ± 12.6 | 85.1 ± 15.8 | T1: 0.001* | |
| T2: < 0.0003* | ||||||
| T3: < 0.0003* |
3.4. Secondary Endpoints
3.4.1. CASA‐Q
All four domains improved significantly from baseline with Provox Life, with T0–T3 changes exceeding the MCID in every domain (COUS +13.3, COUI +19.1, SPUS +20.5, SPUI +21.1); controls remained stable except for transient sputum‐domain gains at T2 (Table 2).
3.4.2. Forced Expectorations and Involuntary Coughs (Tally Sheet)
Forced expectorations were numerically lower in the Provox Life group at every follow‐up visit (T1: 4.1 ± 2.7 vs. 6.7 ± 6.0; T2: 3.8 ± 2.7 vs. 6.9 ± 7.0; T3: 3.3 ± 2.2 vs. 6.6 ± 6.1 per 24 h), with the between‐group comparison at T3 reaching significance (p = 0.023; Table 3). Involuntary coughs were low and similar in both groups throughout (T3: 2.5 ± 2.9 vs. 2.5 ± 5.0; p = 0.325).
TABLE 3.
Forced expectorations and involuntary coughs per 24 h, derived from a 3‐day tally sheet, at each follow‐up visit, with between‐group comparisons.
| Outcome | Group | T0 (Mean ± SD) | T1 (Mean ± SD) | T2 (Mean ± SD) | T3 (Mean ± SD) | p‐value (between groups) |
|---|---|---|---|---|---|---|
| Forced expectorations per 24 h | Control | N/A a | 6.7 ± 6.0 | 6.9 ± 7.0 | 6.6 ± 6.1 |
T1: p = 0.124 T2: p = 0.128 T3: p = 0.023* |
| Provox Life | N/A a | 4.1 ± 2.7 | 3.8 ± 2.7 | 3.3 ± 2.2 | ||
| Involuntary coughs per 24 h | Control | N/A a | 3.9 ± 4.7 | 2.7 ± 3.2 | 2.5 ± 5.0 |
T1: p = 0.925 T2: p = 0.765 T3: p = 0.325 |
| Provox Life | N/A a | 3.2 ± 3.0 | 2.7 ± 2.3 | 2.5 ± 2.9 |
No baseline (T0) tally sheet was collected, by design of the clinical investigation plan; therefore no T0 value and no within‐group change from baseline can be reported for these two variables. The pre‐specified comparison was between arms at study end (T3).
*Statistically significant (p < 0.05); Mann–Whitney U test.
3.4.3. Stomal Management and Pulmonary Complications
In the Provox Life group, dried mucus or crusts at the stoma and stoma cleaning frequency decreased significantly over time (Friedman p = 0.006 and p = 0.005, respectively), with no significant changes in controls. Pneumonia occurred in 10 control patients (11 episodes) versus 3 Provox Life patients (3 episodes) across the study period (T3 rates: 14.8% vs. 2.6%). A single case of tracheitis occurred at baseline and one case of tracheobronchitis at T3, both in the control group; no such events occurred in the Provox Life group. Formal statistical comparison of complication rates was not performed due to low absolute frequencies and pre‐existing baseline differences (Table 4).
TABLE 4.
Patient‐reported stomal and tracheal symptoms and pulmonary complications, by treatment arm and study visit.
| T0 | T1 | T2 | T3 | p‐value (within‐group, across timepoints) | |||||
|---|---|---|---|---|---|---|---|---|---|
| Control | Provox Life | Control | Provox Life | Control | Provox Life | Control | Provox Life | ||
| Stomal management (patient‐reported, preceding 3 months) | |||||||||
| Dried mucus/crusts around stoma | Control: 0.362|PL: 0.006* | ||||||||
| Not at all | 5 | 7 | 9 | 15 | 7 | 12 | 8 | 14 | |
| Very little | 6 | 7 | 4 | 7 | 6 | 13 | 7 | 14 | |
| Quite a bit | 6 | 3 | 5 | 7 | 4 | 2 | 4 | 4 | |
| Quite a lot | 7 | 5 | 5 | 3 | 2 | 1 | 3 | 0 | |
| A lot | 12 | 18 | 13 | 8 | 12 | 11 | 5 | 7 | |
| Stoma cleaning frequency | Control: 0.305|PL: 0.005* | ||||||||
| Not at all | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | |
| Very little | 0 | 2 | 2 | 2 | 3 | 3 | 3 | 5 | |
| Quite a bit | 6 | 2 | 2 | 9 | 6 | 9 | 5 | 11 | |
| Quite a lot | 5 | 4 | 9 | 7 | 4 | 10 | 4 | 3 | |
| A lot | 25 | 32 | 23 | 22 | 18 | 16 | 13 | 19 | |
| Tracheal irritation/dryness | Control: 0.962|PL: 0.793 | ||||||||
| Not at all | 20 | 25 | 22 | 36 | 21 | 37 | 20 | 33 | |
| Very little | 8 | 6 | 4 | 2 | 4 | 2 | 4 | 4 | |
| Quite a bit | 4 | 2 | 3 | 2 | 4 | 0 | 1 | 1 | |
| Quite a lot | 3 | 3 | 2 | 0 | 0 | 0 | 2 | 0 | |
| A lot | 1 | 4 | 5 | 0 | 2 | 0 | 1 | 0 | |
| Windpipe bleeding | Control: 0.997|PL: 0.995 | ||||||||
| Not at all | 30 | 32 | 31 | 38 | 26 | 39 | 20 | 39 | |
| Very little | 4 | 5 | 2 | 2 | 3 | 0 | 7 | 0 | |
| Quite a bit | 2 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | |
| Quite a lot | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | |
| A lot | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Pulmonary complications (patients with ≥ 1 episode) | |||||||||
| Pneumonia, N (%) | 4 (11.1) | 1 (2.5) | 3 (8.3) | 0 (0.0) | 3 (9.7) | 2 (5.1) | 4 (14.8) | 1 (2.6) | — a |
| Tracheobronchitis | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.7) | 0 (0.0) | — a |
| Tracheitis | 1 (2.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | — a |
| Total complications (excl. self‐resolved mucus plugs) | 7 | 2 | 3 | 0 | 3 | 3 | 7 | 1 | — a |
Complication rates were not formally compared between groups because absolute frequencies were low and the control arm already carried more pulmonary complications at baseline; see Section 4.
*Statistically significant (p < 0.05). Within‐group comparisons across timepoints by Friedman test (stomal management, 5‐point ordinal scale referring to the preceding 3 months). Denominators (Control/Provox Life): T0 36/40, T1 36/40, T2 31/39, T3 27/39.
3.4.3.1. Sleep
JSEQ total score fell from 10.4 ± 6.2 to 7.2 ± 4.8 with Provox Life (p = 0.013), with no significant change in controls (11.2 ± 6.8 to 8.5 ± 5.2; p = 0.990); the improvement was driven by the waking several times per night item (Table 5).
TABLE 5.
Jenkins Sleep Evaluation Questionnaire (JSEQ) total scores at each study visit, by treatment arm, with within‐group comparisons against baseline.
| Outcome | Group | T0 (Mean ± SD) | T1 (Mean ± SD) | T2 (Mean ± SD) | T3 (Mean ± SD) | p‐value (vs. T0) |
|---|---|---|---|---|---|---|
| JSEQ total score | Control (N = 36 → 27) | 11.2 ± 6.8 | 10.0 ± 7.0 | 9.1 ± 5.6 | 8.5 ± 5.2 |
T1: > 0.999 T2: > 0.999 T3: 0.990 |
| Provox Life (N = 40 → 39) | 10.4 ± 6.2 | 8.8 ± 5.9 | 8.5 ± 5.4 | 7.2 ± 4.8 |
T1: 0.115 T2: 0.147 T3: 0.013* |
*Statistically significant (p < 0.05). Within‐group comparisons versus baseline (T0) by Friedman test with Bonferroni‐adjusted Wilcoxon signed‐rank post hoc tests. Lower JSEQ scores indicate better sleep. Control N = 36 → 27; Provox Life N = 40 → 39.
3.4.3.2. Quality of Life, Breathlessness, Skin and Voice
The EQ‐5D‐5L index improved with Provox Life at T1 (p = 0.015) and T2 (p = 0.009) but not T3, and the EQ VAS at T2 (p = 0.041); no individual domain and no control comparison reached significance (Table 6). Shortness of breath did not differ between arms, though a numerical trend favored Provox Life (T3: 87.2% vs. 59.3% reporting no dyspnea on stair climbing). Peristomal skin integrity was comparable throughout: frequency, severity, extent, and location of irritation did not differ (all p > 0.05), and irritation resolved within 1–2.8 days after an adhesive change. VHI‐10 scores in the 18 voice‐prosthesis users did not change significantly in either arm.
TABLE 6.
EQ‐5D‐5L index values and EQ visual analogue scale scores at each study visit, by treatment arm, with within‐group comparisons against baseline.
| Outcome | Group | T0 (Mean ± SD) | T1 (Mean ± SD) | T2 (Mean ± SD) | T3 (Mean ± SD) | p‐value (vs. T0) |
|---|---|---|---|---|---|---|
| EQ‐5D‐5L Index value | Control | 0.708 ± 0.252 | 0.678 ± 0.364 | 0.770 ± 0.279 | 0.770 ± 0.279 |
T1: > 0.999 T2: 0.930 T3: 0.562 |
| Provox Life | 0.782 ± 0.212 | 0.851 ± 0.177* | 0.844 ± 0.215* | 0.841 ± 0.203 |
T1: 0.015* T2: 0.009* T3: 0.240 |
|
| VAS scale (0–100) | Control | 72.8 ± 24.8 | 68.2 ± 30.1 | 77.0 ± 20.4 | 73.0 ± 28.8 |
T1: > 0.999 T2: 0.517 T3: > 0.562 |
| Provox Life | 77.6 ± 22.7 | 82.4 ± 20.6 | 87.0 ± 12.8* | 85.1 ± 15.1 |
T1: 0.875 T2: 0.041* T3: 0.493 |
*Statistically significant (p < 0.05). Within‐group comparisons vs. baseline (T0) by Friedman test with Bonferroni‐adjusted Wilcoxon signed‐rank post hoc tests. Higher EQ‐5D‐5L index and EQ VAS values indicate better health status. Control N = 36 → 27; Provox Life N = 40 → 39.
3.4.3.3. Patient Experience
On the comparative questions administered to both arms, Provox Life patients reported improvement significantly more often than controls at T3 across all respiratory, stoma‐hygiene, sleep, and voice‐clarity items (all p ≤ 0.0057), whereas controls most often reported no change. On the satisfaction questionnaire, given to the Provox Life arm only, 35 of 39 patients (89.7%) rated their experience “very good” and 34 of 39 (87.2%) reported no remaining barrier to 24‐h use.
3.5. Adverse Events
Sixty adverse event or device deficiency forms were submitted. Nine non‐serious adverse events were unrelated to the device. Thirty adverse device effects consisted exclusively of anticipated peristomal skin irritation from adhesives or LaryTubes, all resolved by switching adhesive type or adjusting technique; none led to discontinuation. Nine device deficiencies involved anticipated mechanical issues (flange breakage, loose fit). Twelve serious adverse events occurred in 11 patients, all unrelated to the device (including 8 cancer recurrences and 4 pneumonias). No serious adverse device effects occurred.
4. Discussion
To our knowledge, this is the first randomized controlled trial of Provox Life HMEs in patients who had never used HMEs. Near‐continuous 24‐h use was established, with clinically meaningful improvements in coughing, sputum burden, sleep quality, and patient‐reported experience, without compromising skin tolerability.
4.1. Adherence
Mean daily HME use of 23.3–23.9 h/day from the first follow‐up is among the highest adherence rates reported for an HME‐naïve cohort, exceeding the roughly 50% full day‐and‐night use at 3 months with legacy devices [5, 6] and comparable to the increases documented when experienced users switch to Provox Life [1, 2]. This likely reflects the activity‐specific HME variants, improved breathability from the 23 mm design, and individualized adhesive options.
4.2. Pulmonary Health
The significant reduction in forced expectorations at 9 months aligns with the mechanism of HMEs: improved tracheal humidification reduces mucus viscosity and expectoration effort. Parrilla et al. [6] reported reductions from 6.3 to 1.9 per day at 12 weeks in an HME‐naïve cohort, and Bien et al. [5] from approximately 59 to 27–56 per week depending on compliance group. The absence of a between‐group difference in involuntary coughs reflects low baseline frequency in both groups, likely because patients recorded only severe episodes and tracheal irritation was already minimal, as reflected by CASA‐Q scores.
All four CASA‐Q domains improved significantly in the Provox Life group, with changes exceeding published MCIDs at T2 and T3. Although these MCIDs derive from COPD populations [9], the magnitude of change indicates patient‐relevant benefit. These gains exceed those reported by Ward et al. [2] over 6 weeks in patients switching from legacy HMEs, consistent with HME‐naïve patients starting from a higher symptom burden over a longer follow‐up.
4.3. Sleep
The significant improvement in JSEQ total score, absent in controls, is consistent with prior evidence linking nocturnal humidification to reduced tracheal dryness and sleep disruption: Ward et al. [2] confirmed JSEQ improvement with Provox Life, and both Longobardi et al. [1] and Parrilla et al. [6] reported reduced use of sleep medication. The most marked improvement was in nighttime awakenings, implicating continuous nocturnal humidification.
4.4. Pulmonary Complications
The descriptive tendency toward fewer pulmonary complications with Provox Life is biologically plausible: HMEs have been associated with improved mucociliary clearance [13] and, in retrospective and registry data, with lower rates of tracheobronchitis and pneumonia [3]. Low absolute frequencies and baseline differences precluded formal comparison, and randomized evidence does not establish a significant reduction in infectious pulmonary events. The trend is consistent with cost‐effectiveness analyses in which reduced respiratory hospitalizations are the primary source of economic value [14, 15, 16].
4.5. Quality of Life and Patient Satisfaction
The EQ‐5D‐5L composite index showed significant improvements at T1 and T2 despite no individual domain reaching significance, consistent with its known sensitivity to subtle multi‐domain shifts [11]. Most Provox Life patients rated their overall experience “very good,” and the group reported significantly greater improvements than controls across all respiratory, sleep, and stoma‐related comparative questions. Barriers to continued HME use were minimal, with 87.2% of patients reporting none at T3.
4.6. Skin Safety
Skin tolerability is a central concern when introducing adhesive‐based HMEs in an adhesive‐naïve population. Peristomal irritation remained low, transient, and comparable to controls throughout, and all ADEs resolved with adhesive adjustment without discontinuation. The availability of acrylic, hydrocolloid, and hydrogel formulations within the range enables individualized management that sustains adherence without compromising skin integrity [1, 2].
4.7. Limitations
Several limitations should be acknowledged. Blinding was not feasible given device visibility, potentially introducing response bias. The cohort was markedly heterogeneous in time since laryngectomy (3–281 months): a patient recruited months after surgery has breathed through an open tracheostoma only briefly, whereas one recruited decades later carries long‐standing squamous metaplasia and loss of ciliated epithelium, so the reversibility of these changes—and the benefit expected from starting an HME—may differ across the spectrum. A subgroup analysis by time since surgery was not pre‐specified and would be underpowered; the effects reported here are an average across this spectrum and cannot predict benefit for an individual patient at a given interval from surgery. Control‐group dropout was higher than anticipated (11 vs. 2), leaving 27 control completers at T3; dropouts were predominantly cancer‐related, and worst‐case imputation would favor the Provox Life group. Pulmonary complications were ascertained from patient report and routine records rather than protocol‐defined criteria and were not compared statistically, so the pneumonia difference is descriptive only, particularly given the higher control baseline. Both centers are tertiary institutions in São Paulo, limiting generalizability; CASA‐Q MCIDs derive from COPD populations, as laryngectomy‐specific values are unpublished; and seasonal variation cannot be excluded.
5. Conclusions
Near‐continuous 24‐h HME use was established from the first follow‐up and maintained across 9 months in HME‐naïve laryngectomized patients, with clinically meaningful improvements in cough and sputum symptoms and impact, sleep quality, and forced expectorations, and with skin irritation comparable to controls. These findings support Provox Life for initiating pulmonary rehabilitation in this population.
Funding
This study was sponsored by Atos Medical AB, Sweden. The sponsor provided the investigational devices, held the trial database, and performed the statistical analyses; the investigators had full access to the clinical study report and take responsibility for the interpretation of the data and the decision to submit for publication.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Appendix S1: Detailed description of outcome measures, instruments and data collection.
Acknowledgments
The authors thank all patients who participated in this trial and the clinical staff at Instituto de Câncer Dr. Arnaldo and Santa Casa de São Paulo for their dedication throughout the study. This study was sponsored by Atos Medical AB, Sweden.
Artificial Intelligence (AI) tools were not used to conceptualize the study, analyze data, or draw scientific conclusions. AI‐assisted technologies were used strictly for language refinement, grammar editing, and formatting assistance. All authors have reviewed the manuscript and assume full responsibility for the accuracy and integrity of the final content.
Data Availability Statement
The individual de‐identified participant data, data dictionary, and statistical code are held by the sponsor (Atos Medical AB) and are not publicly available.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Appendix S1: Detailed description of outcome measures, instruments and data collection.
Data Availability Statement
The individual de‐identified participant data, data dictionary, and statistical code are held by the sponsor (Atos Medical AB) and are not publicly available.