TO THE EDITOR:
 
An important marker for monitoring disease progression is FEV1, which is considered the single most important predictor of life expectancy in individuals with cystic fibrosis (CF).(1,2) The coefficient of variation (CoV) for FEV1 has been studied in individuals with CF to investigate its relationship with treatment adherence, clinical outcomes, exacerbations, and hospitalizations, as well as a predictor of future decline in FEV1 and of future reduction of functional capacity.(3-5) One study(5) reported that patients who had a variation in FEV1 ≥ 10% in one year had a worse rate of decline in FEV1 in the next two years.
 
The present study aimed to assess the relationship between CoV for FEV1 and the number of days of hospitalization for adult individuals with CF. Secondarily, the relationship of CoV for FEV1 with the number of pulmonary exacerbations and performance in the six-minute walk test (6MWT) was also assessed.
 
This was a retrospective cohort study, conducted under the auspices of the Adult CF Program at the Hospital de Clínicas de Porto Alegre (HCPA), in the city of Porto Alegre, Brazil, over a period of one year (from January to December of 2019). Inclusion criteria were individuals ≥ 18 years of age with a confirmed diagnosis of CF, being regularly monitored at the adult CF outpatient clinic at least three times a year and having undergone at least three spirometry tests at three-month intervals.
 
Clinical and demographic data were extracted from electronic medical records from HCPA. Data on the following variables were recorded at the entry date in the study: BMI, sputum bacteriology, number of exacerbations in the last year, number of hospitalizations in the last year, length of hospital stay (days), 6MWT results, and spirometric parameters. The number of respiratory exacerbations was recorded by determining the number of hospital admissions due to exacerbations and the frequency of oral antibiotic use.
 
Spirometry was performed in accordance with Brazilian guidelines.(6) The variables compiled were FEV1, FVC and FEV1/FVC expressed in liters and percentages of predicted values.(6) The highest and lowest FEV1 values obtained within the study period were extracted, and CoV was calculated as the ratio of standard deviation to the mean for each subject individually and expressed as a proportion.
 
The 6MWT was performed at the HCPA Pulmonary Physiology Unit in accordance with international guidelines. (7) The distance walked on the 6MWT (6MWD) was expressed in meters and in percentage of predicted values.(8) The presence of chronic infection with Staphylococcus aureus, Pseudomonas aeruginosa, or Burkholderia cepacia was recorded. Chronic bacterial infection was defined as three or more positive bacterial isolates during the previous 12 months.
 
For analysis purposes, subjects were classified into two groups according to CoV for FEV1: CoV for FEV1 < 10% and CoV for FEV1 ≥ 10%. The correlations between CoV for FEV1 and other variables were analyzed using Spearman’s correlation coefficient. Categorical variables were compared between the groups using the chi-square test, and data were expressed as number of cases.
 
The electronic medical records of 58 patients who attended the HCPA Adult CF Program during the study period were evaluated, and 47 were considered eligible and included in the study. The remaining 11 patients were excluded because of incomplete records. In the final sample, 20 and 27 patients were male and female, respectively, with a median age of 27 years and a mean BMI of 21.3 kg/m2. Mean FEV1 was 47% of the predicted value, and mean 6MWD was 81% of the predicted value. The median numbers for exacerbations and hospitalizations within a year were 2 and 1, respectively. Regarding the CoV groups, 28 (59.5%) and 19 (40.5%) of the subjects were allocated to the FEV1 ≥ 10% and FEV1 < 10% groups, respectively. The comparisons between the two groups are shown in Table 1.

 
There were no statistically significant correlations of CoV for FEV1 with age at diagnosis and sputum bacteriology. There were statistically significant correlations of CoV for FEV1 with age (ρ = −0.358; p = 0.013); BMI (ρ = −0.423; p = 0.003); total number of exacerbations within a year (ρ = 0.345; p = 0.018); number of days of oral antibiotic use within a year (ρ = 0.356; p = 0.014); length of hospital stay in days within a year (ρ = 0.386; p = 0.007); 6MWD in % of the predicted value (ρ = −0.359; p = 0.013); and SpO2 at the end of the 6MWT (ρ = −0.330; p = 0.024).
 
In this study, CoV for FEV1 ≥ 10%, in comparison with CoV for FEV1 < 10%, was related to a greater number of hospitalizations; that is, a greater number of pulmonary exacerbations and a greater number of days of oral or intravenous antibiotic use throughout the year. The findings are in agreement with those of Heinzmman-Filho et al.,(5) who identified a significant relationship between variations in pulmonary function and the number of hospitalizations. Also, there was a relationship between that variation in one year and a higher number of hospitalizations in the two subsequent years.
 
In general, regular monitoring of pulmonary function in individuals with CF during outpatient visits is essential for establishing early and aggressive treatment of pulmonary exacerbations, seeking to avoid huge variations over time and ensuring greater disease stability.(9) In this context, CoV for FEV1 presents itself as a valid tool for monitoring the abrupt decline of lung function and progression of the disease in individuals with CF.
 
The retrospective nature of the present study, the small number of participants, the lack of assessment of adherence to treatment, and the unavailability of other, more sophisticated, tests, such as imaging tests and the lung clearance index, are some of the limitations of the study. Another important limitation is that only FEV1 was used for the prognostic evaluation of hospitalizations and pulmonary exacerbations.
 
In conclusion, our findings suggest that a CoV for FEV1 ≥ 10% over a year is associated with a greater number of exacerbations and hospitalizations in adult individuals with CF. The use of CoV for FEV1 can benefit the screening and monitoring of disease progression in this population.
 
FINANCIAL SUPPORT
 
This study received financial support from the Fundo de Incentivo à Pesquisa (FIPE, Research Incentive Fund) of the HCPA (Protocol no. 2018-0459).
 
AUTHOR CONTRIBUTIONS
 
EAS: data collection. DR: study design. PTRD: study design, data analysis, and review of the manuscript. BZ: data collection, study design, data analysis, and review of the manuscript. All authors participated in the literature search, drafting of the manuscript, and approval of the final version of the manuscript.
 
CONFLICTS OF INTEREST
 
None declared.
 
REFERENCES
 
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