The Impact of Severe Infectious Pulmonary Exacerbation on fat-free mass in Hospitalized Adults with Cystic Fibrosis

doi:10.21203/rs.3.rs-1522098/v1

Cystic fibrosis (CF) patients experience a continuous acute phase of inflammatory and catabolic state. Longitudinal study to assess the impact of severe infectious pulmonary exacerbation on fat-free mass (FFM) and on the fat-free mass index (FFMI) in adults with CF who required hospital admission. Nutritional assessment using anthropometry and bioimpedance, Visual Appetite Scale (VAS), Kanga Score, functional assessment by spirometry and a 6-minute walk test. Inflammatory biochemical markers cortisol and C-Reactive Protein were also used. Results: The multivariate linear regression analysis identified only sex as an independent variable significantly associated with improvement in the FFMI (B= -1.81, 95% CI= -3.10; -0.51, p=0.008). As for the increase in FFM, two significantly associated independent variables were identified: sex (B= -10.38, confidence interval – 95% CI= -14.70; -6.06, p<0.001); and forced vital capacity (FVC) % of predicted (B=0.13, 95% CI=0.04; 0.23, p=0.006). There was a significant improvement in FFM and FFMI between the start of hospitalization and the 14th day. Gender and FVC % of predicted were responsible for predicting FFM improvement. For the FFMI, the predictive variable of this improvement was gender only, with males having the greatest increase in FFM and FFMI.

Cystic fibrosis (CF) is an autosomal recessive genetic disease that predominantly reaches Caucasians¹. Although it is a multisystemic pathology, the most frequent clinical manifestation is pulmonary, the main determinant of prognosis².

Despite the fact that nutritional management has improved over time, nutritional risk and malnutrition still have a high prevalence in patients with CF. Barni et al.³ studied 73 patients with FC, showing that 24.7% were malnourished. Therefore, malnutrition remains an important issue to be observed in the management of this disease⁴.

Malnutrition in CF is strongly related to high energy expenditure at rest during pulmonary exacerbations^3,5. Inflammatory conditions cause significant pulmonary destruction, and may be responsible for worsening the nutritional status and altering the body composition.The continuous catabolic response affects the fat-free mass (FFM), wearing down inspiratory muscles⁶.

Many studies^{4,5,7,8,9−15} evaluated nutritional status in adult individuals with CF, using body composition and FFM. Among these, only a few^4,7,8,11,13 observed a significant association between forced expiratory volume in the first second (FEV1) and FFM. However, these researches had different objectives, and only one⁷ addressed pulmonary exacerbation.

Therefore, the evaluation of body composition and nutritional status during a pulmonary exacerbation in order to verify the effect of the severity of the exacerbation on FFM and fat-free mass index (FFMI) in adult patients with CF has been little studied.

Thus, the aim of this study was to evaluate the impact of severe acute infectious pulmonary exacerbation on FFM and FFMI in adults with CF who required hospitalization.

Fifty-three adult patients with CF were admitted. Among these patients, 51 met the inclusion criteria and were invited to participate in the research. Four patients were excluded because they refused to participate, 5 by early hospital discharge and 1 was transplanted before the 14th day. Thus, 41 patients completed the study (Fig. 1).

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Among these, 29 (71%) were female. The mean age was 26.0 ± 6.0 years, the median of FEV1 was 40.0% (30.0; 53.0) of the predicted, the mean BMI was 19.8 ± 2.4 Kg/m2, the mean FFMI was 15.3 ± kg/m2, the mean FFM was 41.8 ± 7.3 Kg and the mean of FM 12.0 ± 5.0 Kg. 46.3% were heterozygotes for the F508del mutation, and 31.7% homozygotes. 68.3% of the individuals were colonized by Paeruginosa. Eight of them (19.5%) were active on a lung transplant list at the time (Table 1).

Table 1

– General characteristics of the sample.
Variables	N = 41
Female, n (%)	71 (29,0)
Age, years	26,0 ± 6,0 (18–40)
FEV₁	40,0 (30,0; 53,0)
FVC (%)	63,3 ± 21,0 (34–117)
F508del, % (N)	78,0 (32)
Homozygous F508del, % (N)	31,7 (13)
Heterozygous F508del, % (N)	46,3 (19)
P aeruginosa, % (N)	68,3 (21)
MSSA, % (N)	39,0 (16)
MRSA, % (N)	39,0 (16)
B cepacia, % (N)	34,1 (14)
On lung transplant list, % (N)	19,6 (8)
CFRD, % (N)	39,0 (16)
Exocrine Pancreatic insufficiency, % (N)	87,8 (36)
Oral nutritional supplementation, % (N)	75,6 (31)
BMI (kg/m²), mean ± DT (min-max)	19,8 ± 2,4 (15,6–26,7)
FFMI (kg/m²), mean ± DT (min-max)	15,3 ± 1,9 (12,5–19,8)
FFM (kg), mean ± DT (min-max)	41,8 ± 7,3 (30,7–56,4)
FM (kg), mean ± DT (min-max)	12,0 ± 5,0 (1,3–19,6)
Source. Prepared by the authors. Caption N = Number of participants; FEV1 = forced expiratory volume in the first second; FVC = forced vital capacity; P aeruginosa = Pseudomonas aeruginosa; MSSA = Methicillin-sensitive Staphylococcus aureus;MRSA = Methicillin-resistant Staphylococcus aureus; B cepacia = Burkholderia cepacea; CFRD = cystic fibrosis-related diabetes; BMI = body mass index; SD = Standard Deviation, FFMI = fat-free mass index; FFM = fat-free mass; FM = fat mass.

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The comparative analysis of the variables at admission and on the 14th day showed a significant variation for all variables except for cortisol (Table 2). The variation of the mean FFMI was from 15.3 ± 1.9 Kg/m2 to 15.7 ± 2.0 Kg/m2 (p < 0.001), and the FFM variation was 41.8 ± 7.3Kg for 43.0 ± 7.8Kg (p < 0.001). The variation of FEV1 percent of the predicted presented a median that went from 40.0 (30.0; 53.0) to 45.0 (35.0; 62.0) and p = 0.001.

Table 2

Comparison of clinical and nutritional parameters at the time of hospitalization and on the 14th day.
	Before treatment	After treatment	P Value
Weight (kg), mean ± SD	53,8 ± 7,2	55,5 ± 7,3	< 0,001
BMI (kg/m²), mean ± SD	19,8 ± 2,4	20,4 ± 2,3	< 0,001
FFM (kg), mean ± SD	41,8 ± 7,3	43,0 ± 7,8	< 0,001
FM (kg), mean ± SD	12,0 ± 5,0	12,5 ± 5,1	< 0,001
FFMI (kg/m²), mean ± SD	15,3 ± 1,9	15,7 ± 2,0	< 0,001
Calf circumference (cm), mean ± SD	30,7 ± 3,2	31,0 ± 3,4	< 0,001
Arm circumference (cm), median (IIQ)	25,0 (23,0; 26,0)	25,4 (24,0; 27,0)	< 0,001
Total body water (ml), mean ± SD	30,9 ± 4,5	31,7 ± 4,9	< 0,001
Appetite scale, median (IIQ)	49,0 (27,5; 83,0)	78,0 (69,0; 95,0)	< 0,001
FEV₁ (L), median (IIQ)	1,3 (1,0: 1,9)	1,4 (1,1; 2,1)	< 0,001
FEV₁ (% of predicted), median (IIQ)	40,0 (30,0; 53,0)	45,0 (35,0; 62,0)	0,001
CVF (L), mean ± SD	2,6 ± 0,9	2,8 ± 0,9	< 0,001
CVF (% of predicted), mean ± SD	63,3 ± 21,0	69,5 ± 19,5	< 0,001
DT walk tst (m), mean ± SD	495,1 ± 88,1	522,3 ± 94,7	< 0,001
DT walk test (%of predicted), mean ± SD	66,6 ± 12,3	70,0 ± 13,9	< 0,001
Kanga score (points), mean ± SD	32,1 ± 5,1	19,5 ± 2,9	< 0,001
Cortisol (µg/dl), median (IIQ)	14,2 (11,0; 16,6)	13,2 (10,7; 17,9)	0,532
CRP (mg/dl), median (IIQ)	37,9 (14,7; 70,1)	3,9(1,8; 8,8)	< 0,001
Source: Elaborated by the authors. BMI = body mass index; FFM = fat-free mass; FM = fat mass; FFMI = fat-free mass index; FEC1 L = forced expiratory volume in the first second; FVC = forced vital capacity; DT = distance traveled; CRP = C-reactive protein; SD = Standard Deviation; IIQ = Interquartile interval. T-test for paired samples or Wilcoxon test.

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The analysis of the association between the independent variables of hospital admission and the outcome (FFM and the FFMI on the 14th day) is presented in Table 3. The variables of hospitalization that were significantly associated with FFM on the 14th day were DT in the 6-minute walk test (6MWT) in % of predicted (r = 0.46, p = 0.003), CRP (r=-0.36, p = 0.020, and sex (p > 0.001). The variables that were significantly associated with FFMI on the 14th day were gender (p = 0.020), FEV1% of predicted (r = 0.36, p = 0.025), FVC % of predicted (r = 0.46, p = 0.003), DT in 6MWT% of predicted (r = 0.46, p = 0.003), and CRP (r= -0.36, p = 0.022).

Table 3

Analysis of the association between the independent variables at hospital admission and the outcome FFM and the FFMI on the 14th day of hospitalization)
Independent variables	FFM (kg)	FFMI (Kg/m²)
Pearson Correlation	r (p value)	r (p value)
Age in years	0,16 (0,472)	-0,04 (0,786)
FEV₁% of predictable	0,21 (0,218)	0,36 (0,025)
FVC % of predictable	0,31 (0,054)	0,46 (0,003)
Distance traveled in 6MWT % of predicted	0,46 (0,003)	0,46 (0,003)
Kanga score in points	-0,21 (0,189)	-0,19 (0,233)
Cortisol in µg/dl	-0,18 (0,262)	-0,26 (0,099)
CRP in mg/dl	-0,36 (0,020)	-0,36 (0,022)
Test 1 for independent samples	Mean ± SD	Mean ± SD
Sex	p > 0,001	p = 0,020
Female	40,4 ± 6,7	15,3 ± 2,0
Male	49,4 ± 6,7	16,9 ± 1,6
P. aeruginosa	p = 0,992	p = 0,341
Yes	43,0 ± 7,9	15,5 ± 1,7
No	43,0 ± 7,7	16,2 ± 2,5
MSSA	p = 0,083	p = 0,057
Yes	45,6 ± 7,1	16,5 ± 2,1
No	41,3 ± 7,8	15,3 ± 1,9
MRSA	p = 0,359	p = 0,972
Yes	41,6 ± 7,2	15,7 ± 1,9
No	43,9 ± 8,1	15,7 ± 2,1
B. cepacia	p = 0,300	p = 0,248
Yes	41,2 ± 7,1	15,2 ± 2,1
No	43,9 ± 8,1	16,0 ± 1,1
Mutation	p = 0,642	p = 0,631
Homozygous F508del	41,9 ± 6,1	15,3 ± 1,8
Heterozygous F508del	44,3 ± 9,3	15,8 ± 2,2
Source: Elaborated by the authors. FFM = fat-free mass; FFMI = fat-free mass index; r = Pearson correlation coefficient; FEV1 = forced expiratory volume in the first second; FVC = forced vital capacity; 6MWT = 6-minute walk test; CRP = C-reactive protein; SD = Standard Deviation; P aeruginosa = Pseudomonas aeruginosa; MSSA = Methicillin-sensitive Staphylococcus aureus; MRSA = Methicillin-resistant Staphylococcus aureus; B cepacia = Burkholderia cepacia.

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Table 4 presents the multivariate analysis between the independent variables of hospital admission and the outcome (FFM and the FFMI on the 14th day).

Table 4

Multivariate linear regression analysis between the independent variables of hospital admission and outcome (FFM and FFMI on the 14th day of hospitalization)
Variables	B	CI 95%	p
FFM
Male	-10,38	-14,70; -6,06	< 0,001
FVC % of predicted	0,13	0,04; 0,23	0,006
CPR	-0,04	-0,09; 0,00	0,051
MSSA	-0,246	-4,23; 3,74	0,901
FFMI
Male	-1,81	-3,10; -0,51	0,008
FEV₁	0,03	-0,00; 0,06	0,060
Cortisol	-0,04	-0,16; 0,08	0,499
CPR	-0,01	-0,03; 0,00	0,125
MSSA	-0,12	-1,38; 1,13	0,842
Source: Elaborated by the authors. B = non-standard coefficient, 95% CI = Confidence interval; FEV1 = forced expiratory volume in the first second; FVC = forced vital capacity; CRP = C-reactive protein; MSSA = Methicillin-sensitive Staphylococcus aureus; FFMI = fat-free mass index; FFM = fat-free mass.

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The variables selected with p < 0.1 for the FFM outcome were FVC % of predicted, DT in 6MWT, CRP, sex and methicillin-sensitive Staphylococcus aureus infection (MSSA). However, the DT in 6MWT was excluded from the multivariate model because it presented linearity with FVC. The multivariate regression analysis identified two independent variables significantly associated with FFM: gender (B= -10.38, confidence interval (CI) 95%= -14.70; -6.06, p < 0.001); and FVC (B = 0.13, 95%CI = 0.04; 0.23, p = 0.006).

The variables selected with p < 0.1 for the FFMI outcome were FEV1% of predicted, FVC % of predicted, distance traveled in the 6MWT, cortisol, CRP, sex and MSSA infection. However, the distance traveled in the 6MWT and the FVC were excluded from the multivariate model because they presented collinearity with the FEV1. The multivariate linear regression analysis identified only gender (B= -1.81, 95% CI= -3.10; -0.51, p = 0.008) as an independent variable significantly associated with the FFM.

In this prospective study, it was found that the outcomes FFM and FFMI had a significant improvement between the beginning of hospitalization and the 14th day. The predictors of this improvement for FFM were sex and FVC. For the FFMI, the predictive variable of this improvement was sex only. The analysis showed that the male individuals obtained a higher increase in FFM and a higher improvement in FFMI than the female individuals.

The significant increase in FFM between the beginning and the end of a hospital stay was also evidenced by Bell et al.²⁴, which revealed an average FFM of 42.9Kg on the 1st day, and 43.7Kg (p < 0.001) at the end of hospitalization. These values were very similar to the findings in our study: 41.8 kg at the beginning of hospitalization, and 43.0 kg at the end.

The influence of gender on body composition was evident in the study. Gender was identified as one of the independent variables that were significantly associated with FFM and was the only independent variable significantly associated with FFMI. Our results are in accordance with the findings of Alvarez et al.¹⁰ who studied 32 clinically stable individuals with CF and a control group without CF, and found better nutritional status in males. Sheikh et al.²⁵ concluded that FFMI is more strongly associated with pulmonary function compared to BMI, especially in men. Still, Alicandro et al.⁵ studied 85 young adults with CF retrospectively. Body composition data were compared between two groups, exacerbators and infrequent exacerbators. Male patients classified as frequent exacerbators had lower FFMI (mean of 18.0 kg/m2) compared to infrequent exacerbators (mean of 19.3 kg/m2, p = 0.024). Among the frequent exacerbators, male patients had lower FFM compared to patients who had a lower exacerbation rate.

Significant pulmonary functional improvement was also demonstrated after the treatment of infectious pulmonary exacerbation: FEV1 at hospital admission of 40.0% of the predicted, and 45.0% (p < 0.001) on the 14th day of hospitalization. In the study by Bell et al.²⁴, the functionality was more severely compromised than in our study, but a significant increase in FEV1 was also identified, from 28.5% of predicted to 34.7% of predicted (p < 0.001), between hospital admission and the 15th day after antibiotic treatment. Another study¹⁹ also verified the variation in FEV1 values from 47.7% of predicted at admission to 54.2% of predicted (p < 0.0001) at the end of treatment.

The dimension of pulmonary functional improvement in our study also involved FVC (from 63.3–69.5% of predicted, p < 0.001). These findings were similar to those identified in the study by Bell et al.²⁴ (improvement of 38.8–46.9%, p < 0.001) in the 15th day after antibiotic treatment.

Although cortisol is a stress response hormone, our values did not get a significant improvement when we compared it at the beginning and on the 14th day. In contrast, the study by Ionescu et al.⁷ showed a decrease in its values from 453 to 347, p < 0.05.

In our research, FVC was one of the independent variables significantly associated with FFM. Charatsi et al.⁸ also observed in their sample that patients with FFM depletion had a lower FVC, median of 57%, interquartile interval (IQ) (51;61), versus those with normal FFM, with median FVC of 93%, IQ (82;101.5) and p = 0.001. The study by Sheikh et al.²⁵ observed that only in women, after adjusting for age, the FFM - Z score was positively associated with FVC % of predicted β = 5.5, p = 0.004. In another study²⁶, the FVC % of the predicted was reduced both in the group of normal BMI and low FFMI, group of hidden depletion of FFM, p < 0.05 and in the group of low BMI and low FFMI p < 0,01.

Although studies show a positive relationship between FEV, FFM and FFMI^{7,8,9,11,26−28}, in our sample, FEV1 was not identified as an independent variable significantly associated with FFM, after multivariate linear regression analysis, as well as in King et al.¹² during the evaluation of 58 adult patients with CF within 4 years. Nutritional status, including FFM, was generally preserved, despite the increased severity of lung disease. Two factors were associated with loss of FFM: the highest serum levels of interleukin 6, and the presence of the F508del mutation for CF. In this study, the correlation between the change in FFM and the change in FEV1% of the predicted did not reach statistical significance. Alicandro et al.⁴ after including FEV1 in the multiple linear regression model, observed that no significant association with full-body FFMI β= −0.03, p = 0.80 in men remained.

Several blood biomarkers have been studied against the background of acute infectious pulmonary exacerbation of CF, although none of them are exclusively related to inflammation. CRP is a non-specific acute phase protein that can be easily measured in laboratory. Several studies have shown that CRP is elevated at the onset of pulmonary infectious exacerbation of CF, and decreases significantly until the end of treatment, in proportion to the clinical and functional pulmonary improvement. Despite this response to treatment of exacerbation, no study has shown that CRP is useful in predicting the clinical course of exacerbation²⁹. In the present study, CRP decreased from admission until the 14th day with treatment. However, it was not associated with FFM and FFMI on the 14th day after treatment. Sharma et al.²⁹, as well as our research, compared CRP values at the beginning and at the end of treatment, and a reduction in CRP values was found at the beginning of treatment with an average CRP of 125 (± 69) for an average CRP of 56 (± 51) p < 0.0001 at the end of treatment.

Severe pulmonary infectious exacerbation in CF has a negative impact on the prognosis of the disease. Partly due to the effect of the inflammatory process of exacerbation on muscle catabolism, leading to the depletion of FFM. Thus, the evaluation of the FFMI at the end of hospitalization and the analysis of possible factors associated with this process, could contribute to a better understanding and management of this clinical situation¹². Body composition and FFB in the context of severe pulmonary exacerbation of CF have scarce data in the literature, and a knowledge gap on this topic remains. A better understanding about this process would be of paramount importance for the development of new strategies of nutritional interventions in this population⁸. Nutritional interventions to treat malnutrition should probably be early and not postponed until nutritional deficits are severe enough to be detected using weight-only criteria²⁷.

One of the main limitations of this study was the small sample size and the performance in a single center, restricting the generalization of the data. Secondly, food intake and physical activity were disregarded, influenced by the improvement of muscle mass. Thirdly, tetrapolar electrical bioimpedance was used to evaluate FFM, and not dual-energy x-ray absorptiometry (DXA), which is a method with greater precision. The evaluation of body composition by bioimpedance is usually responsible for overestimating FFM when compared with the gold standard – DXA³⁰. Although our population was compared with itself, avoiding overestimating FFM.

In conclusion, this study found that FFM and FFMI had significant improvement after the treatment of exacerbation. The predictor parameters of this improvement for FFM were gender and FVC percent of predicted. For the FFMI, the predictive variable of this improvement was only gender. Males obtained a higher increase in FFM and a superior improvement in FFMI.

Study design

A prospective cohort study that included CF patients, assessed within the first 48 hours of hospital admission for acute pulmonary infectious exacerbation, and reassessed on the 14th day of hospitalization.

Population

The sample consisted of 41 individuals hospitalized at the Hospital de Clínicas de Porto Alegre (HCPA) in the clinical units and in the emergency room.

Patients included in the study were adults hospitalized for severe infectious exacerbation who agreed to participate in the study voluntarily, and with diagnosis based on the presence of at least one clinical feature of the disease and a positive sweat test (chloride > 60 mEq/l). Cases in which the result of this sweat test was borderline, with the presence of two mutations recognized as causing the disease in the CFTR gene¹⁶ were also included.

Patients admitted to the hospital for another cause, those who did not accept to participate and pregnant women were excluded. Loss of segment and impossibility of applying bioimpedance were also reasons for exclusion.

Ethical Aspects

This project was submitted to the Research Ethics Committee of HCPA and approved with protocol number 18–0468 2018, and to Plataforma Brasil with the protocol number 97777518.2.0000.5327. The volunteers were previously informed about the study and signed the consent form. All experiments were performed in accordance with relevant guidelines and regulations. This study was performed in accordance with the Declaration of Helsinki and the privacy of all participants was respected, and any identified information was shared.

Nutritional Assessment

Anthropometry and body composition

Weight and height were verified on the LD1050 scale (Líder®, São Paulo, Brazil) with accuracy of 50g and with a built-in stationometer to determine BMI (weight in kg, divided by height squared, in meters).

Body composition (fat mass - FM, FFM and water) was analyzed by tetrapolar bioimpedance (Biodynamics 450®). The test was performed in the early hours, according to the manufacturer's instructions; The patients avoided physical exercise in the previous 12 hours, as well as the ingestion of caffeine, teas, black tea and chocolates, and fasted between 4 and 5 hours. Thus, the FFM (FFM in Kg, divided by height squared, in meters) was determined. Arm and calf circumference were also used.

Appetite assessment

Visual Appetite Scale (VAS) was used, with a line from zero to 100 mm. At each end of the scale the following opposites were set: "I had no appetite" and "my appetite was very good", concerning the week preceding the evaluation. The patients were instructed to place a vertical line on the scale, corresponding to their hunger. When measuring the distance between the mark and the left end of the line, a quantification of the patient's hunger was estimated. A score of ≤ 70mm was considered lack of appetite and a > 70mm score was considered normal appetite^17,18.

Assessment Of Pulmonary Exacerbation

The Kanga et al score to assess the severity of exacerbation was used¹⁹, which grades the aggravation of the disease and estimates the improvement or worsening of respiratory function.

Functional Assessment At Admission

Spirometry was performed in the first 2 days of hospitalization and on the 14th day²⁰ with forced vital capacity (FVC) and FEV1 (respectively in liters and percentage of predicted). The variables were expressed as percentage of predicted for gender and age, according to nomograms²¹.

The 6-minute walk test (distance traveled - DT in meters and percentage of predicted) was performed in the first 2 days and on the 14th day²².

Biochemical Analysis

Laboratory tests of cortisol and C-reactive protein (CRP) were performed in the first 2 days and on the 14th day. Cortisol samples were collected between 8 and 10 a.m. and analyzed using the electrochemiluminescence technique. CRP tests were performed using turbidimetric immunoassay technique.

Calculation Of Sample Size

The work of Pichard et al. was used²³. Since the variable FFMI was one of the main outcomes of the study, the power of 80%, the significance level of 0.05, the standard deviation of 1.9 at the beginning of hospitalization, and the 2.1 at the end of hospitalization were considered. As a result, it was found that an "n" of 41 patients would be sufficient to detect a significant minimum difference in FFMI values of 0.9 Kg/m², between the beginning and the end of hospitalization.

Statistical analysis

The statistical procedures were processed in the Statistical Package for the Social Sciences program (SPSS 18.0, Chicago, USA).

For the descriptive analysis frequencies and absolute numbers for categorical variables were used, as well as mean and standard deviation for continuous variables with normal and median distribution, and interquartile interval for continuous variables without normal distribution or ordinal variables.

The Shapiro-Wilks test was performed to assess the normality of the variables. To compare the variables at the time of hospital admission and on the 14th day of hospitalization, Student's t test was used for paired samples (variables with normal distribution), and Wilcoxon test (ordinal variables or without normal distribution).

To assess which variables of hospital admission were associated with the outcome (FFM and FFMI on the 14th day), bivariate analysis was performed using Pearson correlation test (two variables with normal distribution) or Student's t-test for paired samples (one variable with normal distribution and another categorical variable).

After defining which variables were significantly associated with the FFM and FFMI outcomes, the variables with p < 0.10 were selected, which were introduced in the multivariate linear regression model by the enter method. In this model, the variables were examined for multilinearity and, in case of significant identification, the stated variable was excluded from the model.

All statistical tests used were two-tailed. The significance level adopted was p < 0.05.

Author contributions statement

M. N. S. Funding acquisition, Investigation, Methodology, Project administration, Writing - original draft; L. B. J. Resources, Software, Supervision. F. S. F. Formal analysis, Validation, Visualization. B. Z. Investigation, Methodology. P. de T. R. D. Writing, review & editing. All authors reviewed the manuscript.

Data availability

The data sets generated during and/or analysed during the current study are not publicly available for privacy reasons, but are available from the corresponding author on reasonable request.

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No competing interests reported.

The Impact of Severe Infectious Pulmonary Exacerbation on fat-free mass in Hospitalized Adults with Cystic Fibrosis

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Abstract

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Introduction

Results

Discussion

Methods