TO THE EDITOR:
 
Chest wall diseases (CWDs) are characterized by decreased compliance of the chest wall and impaired ventilatory mechanics,(1,2) leading to chronic hypercapnic respiratory failure (CHRF). Patients with kyphoscoliosis and post-tuberculosis sequelae (TbS) have a higher risk of CHRF, depending on the degree of deformity and the age of onset.(3) The clinical presentation of CWDs is usually nonspecific, with a restrictive lung pattern, and sleep-disordered breathing frequently occurs with sleep hypoventilation preceding diurnal respiratory failure.(4)
 
Noninvasive ventilation (NIV) is commonly used to treat CWDs that result in CHRF combined with hypoventilation symptoms (fatigue, morning headache, hypersomnolence, tiredness, or dyspnea) or with the development of related complications. NIV improves hypoventilation symptoms, arterial blood gases (ABG), and pulmonary function test (PFT) results, and it prolongs survival.(5-8) Data on the benefits of short-term NIV are mostly available from uncontrolled trials or studies with larger and more consistent samples of patients with neuromuscular disorders. In a meta-analysis, no significant difference between volume- and pressure-cycled NIV was found in terms of survival.(2) Long-term oxygen therapy (LTOT) alone was associated with worse survival of CWD patients when compared with NIV.(7,8)
 
The expected survival for patients with CHRF due to kyphoscoliosis and TbS are 8 and 3 years, respectively. Factors such as female sex, younger age, higher BMI, higher PaO2, and lower PaCO2 appear to be favorable independent prognostic factors in CWD patients treated with NIV or LTOT.(9)
 
The present study aimed to characterize and evaluate the survival of patients with CWD under follow-up after starting NIV. The primary outcome was survival time since NIV treatment initiation.
 
The authors conducted a retrospective descriptive analysis involving adult patients with CWD on home NIV who were followed up at a pulmonology outpatient clinic between January of 2010 and January of 2022.
 
Clinical data with information about treatment and mortality were collected from the medical records of the patients. PFT and polysomnography results (at baseline) and ABG analysis (at baseline and during NIV treatment) were also obtained. Comorbidities were classified using the Charlson Comorbidity Index (CCI), which predicts mortality using a score that assigns weights (1, 2, 3, or 6) to each condition that a patient has.(10)
 
Statistical analysis was performed using the IBM SPSS Statistics software package, version 28 (IBM Corporation, Armonk, NY, USA). Statistical significance was set at p < 0.05. Categorical and quantitative variables were described as absolute and relative frequencies or as means ± standard deviations. Comparisons between survivors and nonsurvivors were performed with t-tests for independent samples for continuous variables and with chi-squared tests for categorical variables. To analyze the overall sample and to compare survivors according to their diagnosis we used the Mantel-Cox, Breslow, and Tarone-Ware tests. The Cox proportional hazards model was employed to adjust the variables. The selection of independent variables for the multivariate Cox model was based on statistical significance and on curves that presented proportional risks in the univariate analysis.
 
During the 12-year study period, 39 CWD patients on NIV were followed. The mean age was 60.2 ± 16.4 years, and there was a predominance of females (51.3%) and nonsmokers (82.1%). In this cohort of patients with CWD and CHRF, idiopathic kyphoscoliosis (66.7%) and acquired abnormalities of the thoracic cage, mainly TbS (33.3%), were diagnosed. The mean CCI was 2.1 ± 1.1, considering that CWD is a chronic pulmonary disease. Descriptive summary statistics and comparisons between survivors and nonsurvivors are displayed in Table 1.
 

 
A restrictive lung pattern and a simultaneous diagnosis of obstructive sleep apnea were found in 51.3% and in 23.1% of the overall sample, respectively. At baseline (prior to NIV treatment), ABG analysis revealed CHRF (PaO2 = 61.1 ± 9.7 mmHg; and PaCO2 = 59.5 ± 13.0 mmHg). After NIV initiation, both PaO2 (an increase of 14.8 ± 14.5 mmHg) and PaCO2 (a decrease of 15.1 ± 11.7 mmHg) improved.
 
NIV was initiated in the presence of hypoventilation symptoms plus CHRF and in that of acute hypercapnic respiratory failure in 53.8% and in 46.2% of the sample, respectively. Patients with hypoventilation due to other respiratory diseases were excluded from the study. Most of the patients underwent pressure-targeted mode of NIV (87.2%) and wore facial masks (79.5%). LTOT was simultaneously used with NIV in 66.7% of the patients, with a mean flow rate of 1.8 ± 0.8 L/min.
 
In our sample, the 12-year and 5-year mortality rates were 46% and 15%, respectively. Mortality rates were higher in patients with TbS than in those with kyphoscoliosis (54% vs. 42%). The median survival time since NIV initiation was 146.0 ± 19.4 months, and no differences were found between the groups of diagnosis.
 
Nonsurvivors presented with more comorbidities, lower FVC and FEV1 in % of predicted values, lower respiratory disturbance index, and higher PaCO2 at baseline than did survivors. Older and female patients using LTOT showed a trend toward higher mortality, but the difference was not statistically significant.
 
Univariate Cox analysis identified the following variables as significant predictors of mortality: CCI (hazard ratio [HR] = 1.70; p = 0.02), PaO2 after NIV initiation (HR = 0.95; p = 0.05) and PaCO2 at baseline (HR = 1.03; p = 0.01). No significant differences were found regarding demographic variables, diagnosis, PFT results, polysomnography results, NIV mode, mask use, and LTOT use. In the multivariate Cox analysis, lower PaO2 after NIV initiation (HR = 0.93; p = 0.01) and higher PaCO2 at baseline (HR = 1.07; p = 0.01) were associated with mortality.
 
This retrospective study helps support the benefits of long-term NIV on morbidity and mortality in patients with CWD. This study showed a median survival time of 12 and 13 years, respectively, for patients with kyphoscoliosis and TbS who were treated with NIV; therefore, survival was extended in 4 and 10 years, respectively, when compared with previous evidence.(9)
 
Some of the potential strengths of the design of this study were the homogeneity of the cohort and the long follow-up period. To the best of our knowledge, this is the largest cohort of CWD patients on NIV reported by a Portuguese center. This study has limitations, such as the small sample size, and the effects of NIV on quality of life and lung function were not evaluated. The data presented herein reflect the clinical expertise of a single institution and may not be fully representative of practices elsewhere.
 
In conclusion, the findings of the present study suggest that patients with CWD on NIV may have their risk of mortality reduced, which can be predicted based on PaCO2 at diagnosis and on PaO2 after NIV initiation.
 
AUTHOR CONTRIBUTIONS
 
JAB: study conception and design; data collection; statistical analysis; and drafting and review of the manuscript. CR and FF: critical review of the manuscript. All of the authors approved the final version of the manuscript.
 
CONFLICTS OF INTEREST
 
None declared.
 
REFERENCES
 
1.            Duiverman ML, Wijkstra PJ. Chronic NIV in chest wall disorders. In: Simonds AK, editor. ERS Practical Handbook Noninvasive Ventilation. Sheffield, UK: European Respiratory Society; 2015. p.182-189.
2.            Annane D, Orlikowski D, Chevret S. Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders. Cochrane Database Syst Rev. 2014;2014(12):CD001941. https://doi.org/10.1002/14651858.CD001941.pub3
3.            Casas A, Pavía J, Maldonado D. Respiratory muscle disorders in chest wall diseases [Article in Spanish]. Arch Bronconeumol. 2003;39(8):361-366. https://doi.org/10.1016/S0300-2896(03)75404-0
4.            Hilbert J. Sleep-Disordered Breathing in Neuromuscular and Chest Wall Diseases. Clin Chest Med. 2018;39(2):309-324. https://doi.org/10.1016/j.ccm.2018.01.009
5.            Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation--a consensus conference report. Chest. 1999;116(2):521-534. https://doi.org/10.1378/chest.116.2.521
6.            McKim DA, Road J, Avendano M, Abdool S, Cote F, Duguid N, et al. Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(4):197-215. https://doi.org/10.1155/2011/139769
7.            Gustafson T, Franklin KA, Midgren B, Pehrsson K, Ranstam J, Ström K. Survival of patients with kyphoscoliosis receiving mechanical ventilation or oxygen at home. Chest. 2006;130(6):1828-1833. https://doi.org/10.1378/chest.130.6.1828
8.            Buyse B, Meersseman W, Demedts M. Treatment of chronic respiratory failure in kyphoscoliosis: oxygen or ventilation?. Eur Respir J. 2003;22(3):525-528. https://doi.org/10.1183/09031936.03.00076103
9.            Chailleux E, Fauroux B, Binet F, Dautzenberg B, Polu JM. Predictors of survival in patients receiving domiciliary oxygen therapy or mechanical ventilation. A 10-year analysis of ANTADIR Observatory. Chest. 1996;109(3):741-749. https://doi.org/10.1378/chest.109.3.741
10.          Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prog-nostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383. https://doi.org/10.1016/0021-9681(87)90171-8