Lung Function Decline in Cystic Fibrosis Patients and Timing for Lung Transplantation Referral

doi:10.1378/chest.126.2.412

Chest

Volume 126, Issue 2, August 2004, Pages 412-419

https://doi.org/10.1378/chest.126.2.412 Get rights and content

Study objectives:

To determine risk factors associated with an accelerated decline in lung function in cystic fibrosis (CF), and whether longitudinal changes in FEV₁ would be a better predictor of the need for referral for lung transplantation than any single value for FEV_1.

Design:

The rate of decline in pulmonary function was determined by standard linear regression from each patient's calendar year's best percentage of predicted FEV₁ (%FEV₁) over at least 4 years, and patients were classified into three cohorts based on their rate of decline. Differences between groups in age, weight-for-age z score, gender, genotype, pancreatic status, diabetes, and the presence of various lung microbial isolates were analyzed. A subset of 30 patients referred for lung transplantation were further analyzed, and a prediction model for lung transplantation referral was created using the patient's rate of decline in lung function, the mean waiting time for donor organs, and the average level of lung function of patients prior to lung transplantation.

Patients:

One hundred fifty-three patients with CF followed up at the Washington University Adult Cystic Fibrosis Center.

Results:

Younger age, malnutrition, and concurrent infection with both Pseudomonas aeruginosa and Staphylococcus aureus were significant (p < 0.05) risk factors for rapidly declining lung function. Among patients with rapidly declining lung function, referral for lung transplantation would have occurred 8.4 months earlier than actual referral age (p < 0.05) if the prediction model had been used, possibly resulting in additional patient salvage in several cases.

Conclusions:

Rate of decline in lung function should be routinely evaluated in patients with CF, and a prediction model utilizing the rate of decline in %FEV₁, and the median regional waiting period for donor lungs for patients with CF may assist in the timing of referral for lung transplantation and more rapidly declining lung function.

Section snippets

Methods and Materials

We evaluated the medical records of all 174 patients with CF followed up at the Washington University Adult Cystic Fibrosis Center between 1995 and 2002 for whom pulmonary function data spanning at least 4 years were available (n = 153). Longitudinal trends in FEV₁ were evaluated using the percentage of predicted FEV₁ (%FEV₁). Percentage of predicted values were calculated from the equations of Knudson et al.⁴ The best %FEV₁ of each calendar year, as suggested by others,⁵ was used in a

Results

The mean rate of decline in %FEV₁ for all patients was – 3.89 ± 4.11%/yr. This number is similar to results of similar analyses by others.¹¹¹²¹³¹⁴¹⁵ The distribution is shown in Figure 1.

Since 2 SEs about the mean defines the 95% confidence limits for the true mean, patients with rates of decline greater or less than these limits are not likely to have an “average” rate of decline in pulmonary function. The rate of decline was greater than the above overall group mean + 2 SE in 54 patients

Discussion

While a decline in lung function is typical of almost all patients with CF, the rate of decline is highly variable. In addition, Menendez et al¹⁶ noted different patterns of decline, which they characterized as early linear decline, no change, no change followed by linear decline, or no distinguishable pattern. In the current study, the overall rate of decline in lung function in our adult patients was similar to that published in other series.¹¹¹²¹³¹⁴¹⁵ Moreover, we also observed patterns of

Conclusions

The rate of decline in lung function (using the year's best %FEV₁) should be routinely evaluated in patients with CF. This analysis can be easily performed by any caregiver for any patient with the use of commonly available spreadsheet applications. Patients with CF should be referred for transplantation at a time when based on their rate of decline in lung function, the expected time for their %FEV₁ to reach 20% equals the average local waiting time for donor lungs, or when the baseline %FEV₁

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Clinical, paraclinical, and genetic profile of patients with cystic fibrosis from Colombian Caribbean
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Cystic fibrosis (CF) is a serious autosomal recessive disorder. Early diagnosis, comorbidity prevention, and control are cornerstones for a quality life and for improving life expectancy. In Colombian Caribbean, where there is a genetically admixed population, CF is an orphan disease affecting children and adults, and it remains a challenging issue to be addressed carefully. This work describes the genetic, clinical, and paraclinical profiles of CF patients from Cartagena de Indias, Colombia.
Thirty-six patients were included in the study. The subjects were identified and evaluated through the Regional Program for CF patients. CFTR gene mutations, anthropometric parameters, microbiological infections, and pulmonary function were analyzed. Data on demographic parameters, pharmacological treatments, and comorbidities were reported. Frequency and percentages were established for the categorical variables and mean or median for the quantitative variables. In addition, comparisons were made by sex.
The average age of the patients was 11.9 ± 5.3 years and the median age at diagnosis was 14 months. 55.5% were women and 44.5% were men. The mean values for weight, height, and body mass index were 35 ± 17.6 kg, 139.9 ± 28 cm, and 16.5 ± 2.9 kg/m², respectively. The clinical manifestations that occurred more frequently were steatorrhea (65.4%) and recurrent pneumonia (46.2%). Chronic airway infection with Pseudomonas aeruginosa was identified in 71.4% of the cases and the p.F508del mutation was found in 47.2% of the subjects.
The current profile of CF patients from the Colombian Caribbean showed some concerning features, such as nutritional status; however, progress in early diagnosis and clinical follow-up could contribute to improve the general conditions of patients. It is necessary to continue efforts to increase the life expectancy and quality of life of the patients.
Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression
2021, Journal of Cystic Fibrosis
Citation Excerpt :
Although pregnancies do not appear to accelerate disease progression, and from our data, patients with PI and chronic PA infection experienced a decline in PEx during pregnancy, Schechter et al. suggested that they may lead to more PEx, more illness-related visits, and a decrease in quality of life [22]. Prior to novel modulator therapies, the annual FEV1 decline had been 2-3% per year [23]. Similar to other studies, this rate was not affected by pregnancies [24,25].
With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes.
To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression.
A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV₁) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter.
Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV₁ and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV₁ was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants.
Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.
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2021, Encyclopedia of Respiratory Medicine, Second Edition
Selection criteria for lung transplantation have evolved significantly over the last 3 decades and there are few absolute contraindications. A number of relative contraindications exist but most can be managed effectively given early referral, depending on the experience of the individual transplant unit. Effective communication between the referral source and the transplant unit is crucial to enable optimum outcomes. Successful lung transplantation is built on team work and each craft group plays a critical role in achieving the best results. This chapter will outline the key developments which have led to the current position regarding selection criteria and show the chronology of approach. Given that key consensus documents exist to guide referral and selection of potential candidates this particular chapter will attempt to analyze the body of work which underpins those decisions and show how the global lung transplant community has worked cohesively to improve outcomes for patients who might benefit from their services.
Average rate of lung function decline in adults with cystic fibrosis in the United Kingdom: Data from the UK CF registry
2021, Journal of Cystic Fibrosis
Rate of change in lung function is used as a measure of disease progression and a predictor of mortality in individuals with cystic fibrosis (CF). The aim of this study was to determine the national rate of decline in percent predicted Forced Expiratory Volume in 1 second (ppFEV₁) in adults in the UK accounting for age, sex and pancreatic status.
Data on ppFEV₁ for adults with CF, excluding those post lung transplantation, was extracted from the UK CF registry between 2015 and 2017. Multilevel modelling was conducted to calculate the annual rate of change in ppFEV₁ accounting for age, sex and pancreatic status.
Overall annual ppFEV₁ decline was -1.52% (95% CI: -1.66 to -1.38%) and -0.55% (95% CI: -0.86 to -0.23%) in pancreatic insufficient (PI) and sufficient (PS) adults respectively. In PI individuals, females had a greater rate of decline in ppFEV₁. There were differences between age groups. The fastest rate of decline was observed in the 18–28 years group, declining -1.76% (95% CI: -2.06 to -1.46) and -1.61% (95% CI: -1.91 to -1.31) per year in PI females and males respectively. The pattern between the sexes and age categories was more inconsistent in the PS group.
The average annual rates of decline in lung function in adults with CF in the UK are similar to reports from other large international cohorts. Pancreatic status has a marked impact on average rate of decline. Younger adults, especially females, have a faster rate of decline and need close monitoring.
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Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates
2023, Journal of Medical Microbiology

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: Supported in part by a grant from the Cystic Fibrosis Foundation.

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Chest

Study objectives:

Design:

Patients:

Results:

Conclusions:

Section snippets

Methods and Materials

Results

Discussion

Conclusions

References (20)

Lung transplantation for cystic fibrosis: special considerations

Chest

Gender differences in cystic fibrosis:Pseudomonas aeruginosainfection

J Clin Epidemiol

Clinical outcome after earlyPseudomonas aeruginosainfection in cystic fibrosis

J Pediatr

Colonization of the respiratory tract withPseudomonas cepaciain cystic fibrosis: risk factors and outcomes

Chest

Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis

J Pediatr

Long-term patterns of obstructive lung disease in cystic fibrosis

Chest

Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years

J Pediatr

Timing of referral for lung transplantation for cystic fibrosis: overemphasis on FEV₁may adversely affect overall survival

Chest

Patient registry 2001 annual data report

Prediction of mortality in patients with cystic fibrosis

N Engl J Med

Cited by (122)

Clinical, paraclinical, and genetic profile of patients with cystic fibrosis from Colombian Caribbean

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression

Lung Transplantation: Recipient Selection

Average rate of lung function decline in adults with cystic fibrosis in the United Kingdom: Data from the UK CF registry

MODELING CYSTIC FIBROSIS PATIENT PROGNOSIS: NOMOGRAMS TO PREDICT LUNG TRANSPLANTATION AND SURVIVAL PRIOR TO HIGHLY EFFECTIVE MODULATOR THERAPY

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Chest

Clinical InvestigationsCYSTIC FIBROSISLung Function Decline in Cystic Fibrosis Patients and Timing for Lung Transplantation Referral

Study objectives:

Design:

Patients:

Results:

Conclusions:

Section snippets

Methods and Materials

Results

Discussion

Conclusions

Chest

J Clin Epidemiol

J Pediatr

Chest

J Pediatr

Chest

J Pediatr

Chest

Patient registry 2001 annual data report

Prediction of mortality in patients with cystic fibrosis

N Engl J Med

Clinical Investigations
CYSTIC FIBROSIS
Lung Function Decline in Cystic Fibrosis Patients and Timing for Lung Transplantation Referral