Relationship between pulmonary exacerbations and daily physical activity in adults with cystic fibrosis

A cohort of 60 adult patients with CF was recruited at the Policlinico Umberto I Hospital, Sapienza University of Rome, Italy and at the Royal Brompton Hospital, London, UK. Data on pulmonary exacerbations in the preceding 12-month period, demographic and clinical characteristics, and daily physical activity levels were collected at the time of enrolment. The study was approved by the Ethics Committee of Policlinico Umberto I Hospital, with approval number 582/11, and Royal Brompton Hospital, protocol number 07/H0711/125.

Adult patients attending a CF outpatient clinic were approached for participation in the study between January 2012 and May 2014. Patients were included if they were ≥18 years of age and had a confirmed diagnosis of CF based on genetic testing showing two CF-causing mutations and/or two documented sweet chloride values >60 mEq/L. Patients were excluded if they had experienced a pulmonary exacerbation within 4 weeks of the study period; were on the waiting list for lung transplantation; or had undergone lung transplantation. Baseline data were collected at the time of study entry.

After obtaining written informed consent and appropriate screening of medical history, we collected data on age, sex, height, weight, body mass index (BMI), chronic infections and CF comorbidity (pancreas insufficiency and CF-related diabetes). We also collected information on number of pulmonary exacerbations and exacerbation treatment in the preceding 12-month period. Exacerbation events were ascertained through a review of electronic records and hospital charts. To check if there were exacerbations that had not been captured in the health records, direct patient interview was also conducted. Specifically, we collected data on the number of pulmonary exacerbations in the past year requiring oral or intravenous antibiotics. Even if pulmonary exacerbation remains a subjective diagnosis, and unifying definition is still lacking within the CF literature [ 19, 20], pulmonary exacerbations were defined as acute or subacute worsening of respiratory symptoms, severe enough to warrant oral or intravenous antibiotics. Antibiotic treatment was at the discretion of the treating physician. All patients underwent pulmonary function testing at the time of study entry, which was performed according to American Thoracic Society (ATS) standards, and expressed as percentages of predicted values [ 21].

Physical activity was assessed at the time of the study enrolment, using a multi-sensor armband (SenseWear Pro3 Armband; BodyMedia, Pittsburgh, PA, USA) that the patients wore for at least 5 full consecutive days when they were at home. Physical activity data were recorded for 5 full days for all patients and reported as the average of 5 days.

The device was positioned on the upper right arm over the triceps muscle at the midpoint between the acromion and olecranon processes. Patients were instructed to wear the armband day and night and only to remove it for bathing or showering. Patients were also asked to continue any respiratory medications and any of their normal activities. The sensor contained a biaxial accelerometer, galvanic skin response sensor, heat flux sensor, skin temperature sensor, and a near-body ambient temperature sensor from which the data were stored every minute. Using specific software (version 6.1), these variables, as well as body weight, height, handedness and smoking status (smoker or non-smoker), were used to estimate energy expenditure (EE). Several aspects of EE, including total energy expenditure (TEE) and active energy expenditure (AEE), were also calculated. The intensity of physical activity, expressed in metabolic equivalents (METs), total physical activity duration, the number of steps, time lying down, and sleep duration were also measured. The outputs obtained from the armband were time spent in physical activity at different intensities, and the definitions for activity levels based on METs were those used by Troosters et al . [ 16]. The time spent with an EE of 3–4.8 METs was considered mild activity (e.g., walking at normal speed, or carrying out light household work); time spent at 4.8–7.2 METs was considered moderate activity (e.g., brisk walking or cycling); and activities with EE >7.2 METs were considered vigorous (e.g., running or activity with training effects when applied for a sufficient length of time and at an appropriate training frequency) [ 22]. Studies performed in patients with CF have validated the use of the SenseWear Armband and have shown that the hypersalinity of sweat does not affect the accuracy of EE estimation, and have demonstrated that the device provides an accurate estimate of physical activity in the free-living environment [ 23, 24]. Finally, it was reported in CF that 5 days monitoring was enough to assess habitual PA and that PA levels were similar through the week (i.e., weekdays versus weekend days) [ 15, 16].

Baseline characteristics of the group were obtained on the day of enrolment. Patients were grouped according to their exacerbation status in the preceding year: (1) <1 exacerbation/year; (2) 1–2 exacerbations/year; and (3) >2 exacerbations/year. The groupings were made a priori before commencing study analysis, based on data in the literature [ 10]. We selected three exacerbation groups to determine if there was different daily activity related to pulmonary exacerbation frequency. Once established, the exacerbation groupings were used as predefined thresholds and subsequent analysis were performed using these thresholds.

Categorical data are presented as percentages, and comparisons were performed using the χ ² or Fisher’s exact test. Male and female patients were compared using an unpaired t test.

Physical activity variables, age, sex, BMI, FEV ₁ expressed as percentage of predicted (FEV ₁% predicted), genotype, CF comorbidity (diabetes and pancreatic insufficiency) and infection with Pseudomonas aeruginosa were compared among pulmonary exacerbation groups, using statistical parametric and non-parametric tests and a multivariate model (ANOVA).

Baseline characteristics and pulmonary function data for the group as a whole are shown in Table  1. A mean of 2.38 exacerbations per patient was reported: 2.92 in women versus 2.0 in men, P = 0.13. Men were older than women and had lower FEV ₁ % predicted ( P = 0.04), while women tended to have more exacerbations/year. Habitual activity levels were significantly lower in women than men (Table  2). Compared with men, women had reduced TEE in daily life ( P < 0.0001) and AEE ( P = 0.01) and lower average METs ( P < 0.05). Activities with vigorous intensity were lower in women ( P = 0.01). Similarly, there was a trend for less activity at moderate intensity [women 10 (6–24) min vs 19 (9–33) min for men; P = 0.16) and less duration of physical activity (women 184 ± 115 min vs 233 ± 149 min for men, P = 0.17). After adjusting for other covariates, these physical activity variables remained significantly higher among male patients.

Eleven patients had <1 exacerbation/year, 31 had 1–2 exacerbations/years, and 18 had >2 exacerbations/year (Table  3). The group with more frequent exacerbations had a higher proportion of patients with a severe genotype ( P = 0.001), pancreatic insufficiency ( P = 0.006), CF-related diabetes ( P = 0.006), and had chronic P. aeruginosa infection ( P = 0.008). Patients who experienced >2 exacerbations/year had lower baseline FEV ₁; both expressed as absolute values and % of predicted ( P = 0.01 and P = 0.05, respectively). As shown in Table  3, compared with patients who had <1 or 1–2 exacerbations/year, the group with >2 exacerbations/year spent less time in daily physical activity ( P = 0.01). Daily activities at mild intensity were markedly reduced in patients with >2 exacerbations/year ( P = 0.01). AEE (i.e., number of calories per day due to physical activity) and average METs were lower in the group with more frequent exacerbations ( P = 0.03 and P = 0.01, respectively). Conversely, there was no significant difference for activities with at least moderate and vigorous intensity among the three groups (Table  3).

There was however, no association between the number of pulmonary exacerbations in the preceding year and physical activity variables when corrected for clinical covariates (age, sex, BMI, FEV ₁% predicted, infection with P. aeruginosa, genotype, diabetes and pancreatic insufficiency). Daily physical activity was independently associated with gender and airflow obstruction. TEE and AEE were related to sex ( P < 0.0001 and P = 0.01, respectively). Physical activities above the threshold of moderate (4.8–7.2 METs) and vigorous (>7.2 METs) intensity were also related to sex and FEV ₁% predicted ( P = 0.007 and P = 0.04, respectively). Finally, the number of steps was lower in those with a lower FEV ₁% predicted, although this was not significant ( P = 0.09).