Abstract
We conducted a descriptive analysis of people with CF 40 years of age and older using CF Foundation Patient Registry data from 2022 to provide a current estimate of the population size and characteristics. We summarized demographic details including biological sex, race, ethnicity, insurance and employment status. Clinical data including body mass index, lung function, respiratory infections, hospitalization rates, prevalence of CF-related complications and CF therapy prescriptions were collated. A total of 5,243 individuals aged 40 years or older contributed data to the CFFPR: 2,687 (51%) people aged 40–49 years; 1,410 (27%) people aged 50–59 years; and 1,146 (22%) people aged 60 years or older. The ≥60 year old group have unique characteristics compared to younger individuals, with later diagnosis of CF, greater proportion of females (58%). These results highlight heterogeneity in the older CF adult population and the need to develop and individualize CF care practices.
Introduction
Cystic fibrosis (CF) was historically considered a pediatric disease. Thirty years ago, children aged 18 years or younger comprised 70% of the prevalent CF population and median predicted survival age was approximately 30 years for those born between 1990–1994 (1). Improvements in early diagnosis, nutrition, and the introduction of CFTR modulators have resulted in increased median predicted survival for people with cystic fibrosis (PwCF) (2), now estimated at 56 years of age for people born between 2018–2022 in the United States (US) (1). As of 2022, adults represented nearly 60% of all Americans living with CF (1). Given the complexity of CF care, combined with increasing risk of age-related comorbidities (3–5), the objective of this study was to characterize a wide range of clinical indicators for adults with CF >40 years of age. Such data are needed to plan the design of research studies, inform CF care delivery practices and quantify the population impacted by future policy decisions.
Methods
The Cystic Fibrosis Foundation Patient Registry (CFFPR) maintains data on PwCF who consent to participate at Cystic Fibrosis Foundation (CFF) accredited care centers (6). Individuals with a reported CF diagnosis and aged ≥40 years in 2022 were included in this report.
Individuals were classified into three groups by age (40–49, 50–59, ≥60 years) as of December 31, 2022. Patient characteristics including airway microbiology, nutrition, pulmonary function, complications, screening tests, insurance and employment status, and hospitalizations were reviewed. Pulmonary function was assessed using percent predicted forced expiratory volume in one second (ppFEV1) based on the 2022 Global Lung Function Initiative reference equations (7). Categorical variables were summarized as percentages and continuous variables using mean and standard deviation or median and interquartile range (IQR). Analysis was implemented in SAS version 9.4. This study was classified as exempt from human subjects review by the Advarra Institutional Review Board.
Results
Individuals ≥40 years of age accounted for 27% of the adult US CFFPR population in 2022. A total of 5,243 individuals with CF aged 40 years or older in 2022 were included in the analysis. By age group, 2,687 (51%) were 40–49 years, 1,410 (27%) 50–59 years, and 1,146 (22%) were ≥60 years old. By the end of 2022, 84 individuals died, with 39 deaths occurring post-transplant.
Several summary statistics highlight characteristics that distinguish PwCF ≥60 years of age from younger individuals (Table 1). Those ≥60 years were disproportionately female (58%); had the lowest prevalence of F508del CFTR genotypes (31% with no F508del alleles); and older age of CF diagnosis (median: 51.0 years (IQR: 18.4; 62.4). Among the ≥60 age group, 10% were post-lung transplant compared to 15% and 18% among the younger age groups. PwCF aged ≥60 years had a higher prevalence of Medicare (60%) and lower prevalence of private insurance (51%) compared to younger individuals, and 48% were classified as retired. The prevalence of NTM positive airway cultures was highest among PwCF ≥60 years of age (19%).
Table 1.
Descriptive characteristics of people with cystic fibrosis ≥40 years of age, 2022
| 40–49 years old | 50–59 years old | ≥60 years old | |
|---|---|---|---|
| Total, n (%) | 2687 (51.3) | 1410 (26.9) | 1146 (21.9) |
| Female sex, n (%) | 1234 (45.9) | 657 (46.6) | 669 (58.4) |
| F508del, n (%) | |||
| Homozygous | 1159 (43.5) | 432 (31.2) | 114 (10.2) |
| Heterozygous | 1143 (42.9) | 690 (49.9) | 663 (59.1) |
| Other | 365 (13.7) | 261 (18.9) | 344 (30.7) |
| Race, n (%) | |||
| White | 2557 (95.2) | 1362 (96.6) | 1110 (96.9) |
| Black | 79 (2.9) | 25 (1.8) | 13 (1.1) |
| Other† | 51 (1.9) | 23 (1.6) | 23 (2.0) |
| Hispanic Ethnicity, n (%) | 91 (3.4) | 48 (3.4) | 24 (2.1) |
| Median age at diagnosis in years (IQR) | 1.5 (0.3, 12.0) | 9.1 (1.0, 33.7) | 51.0 (18.4, 62.1) |
| Insurance, n (%)* | |||
| Private | 1864 (69.4) | 992 (70.4) | 579 (50.5) |
| Medicare | 682 (25.4) | 384 (27.2) | 690 (60.2) |
| Medicaid | 440 (16.4) | 173 (12.3) | 89 (7.8) |
| Tricare/Military/Indian Health/Other | 207 (7.7) | 111 (7.9) | 98 (8.6) |
| Employment (not mutually exclusive), n (%) | |||
| Part-time | 321 (12.1) | 119 (8.6) | 97 (8.7) |
| Full-time homemaker | 149 (5.6) | 67 (4.9) | 35 (3.1) |
| Full-time employment | 1402 (53.0) | 637 (46.2) | 208 (18.6) |
| Unemployed | 236 (8.9) | 118 (8.6) | 67 (6.0) |
| Disabled | 639 (24.1) | 403 (29.2) | 229 (20.5) |
| Retired | 21 (0.8) | 92 (6.7) | 540 (48.3) |
| Median ppFEV1 (IQR) | 72.9 (52.2, 90.0) | 68.2 (50.5, 86.6) | 70.5 (51.9, 89.4) |
| Lung Function ppFEV1, n (%) | |||
| <40 | 234 (10.3%) | 140 (12.1%) | 80 (7.8%) |
| 40–70 | 737 (32.4%) | 419 (36.2%) | 381 (37.1%) |
| 70–90 | 882 (38.8%) | 403 (34.8%) | 351 (34.2%) |
| >90 | 264 (11.6%) | 111 (9.6%) | 121 (11.8%) |
| Missing | 159 (7.0) | 84 (7.3) | 94 (9.2) |
| History of lung transplant, n (%) | 415 (15.4) | 257 (18.2) | 120 (10.5) |
| Median BMI value, kg/m2 (IQR) | 24.7 (22.1, 27.9) | 25.2 (22.6, 28.6) | 24.8 (21.9, 28.3) |
| Hospitalizations | |||
| Average IV treated PEx (SD) | 0.2 (0.6) | 0.2 (0.6) | 0.2 (0.6) |
| Average total hospitalizations (SD) | 0.3 (0.8) | 0.3 (0.8) | 0.3 (0.7) |
| Average nights hospitalized for PEx (SD) | 13.6 (21.8) | 15.5 (18.4) | 12.8 (16.1) |
| Bacterial culture recorded in Registry, n (%) | 2154 (80.2) | 1112 (78.9) | 941 (82.1) |
| Pseudomonas aeruginosa | 1097 (50.9) | 512 (46.0) | 433 (46.0) |
| Methicillin-resistant Staphylococcus aureus | 252 (11.7) | 121 (10.9) | 82 (8.7) |
| Methicillin-sensitive Staphylococcus aureus | 639 (29.7) | 262 (23.6) | 189 (20.1) |
| Mycobacterial culture recorded in Registry, n (%) | 1208 (45.0) | 657 (46.6) | 596 (52.0) |
| Any NTM detected, n (%) | 102 (8.4) | 68 (10.4) | 112 (18.8) |
| Complications, n (%) | |||
| Any diabetes (CFRD, Type 1, Type 2) | 1224 (45.6) | 682 (48.4) | 376 (32.8) |
| Any diabetes among those post-transplant | 330 (79.5) | 195 (75.9) | 87 (72.5) |
| Liver disease, cirrhosis/non-cirrhosis | 138 (5.3) | 65 (4.8) | 33 (3.0) |
| ABPA | 133 (5.1) | 65 (4.8) | 53 (4.9) |
| Asthma | 802 (31.0) | 418 (30.8) | 346 (31.7) |
| Anxiety or Depression | 1141 (44.2) | 526 (38.8) | 384 (35.2) |
| Arthritis | 217 (8.2) | 126 (9.1) | 148 (13.3) |
| Osteopenia | 720 (27.2) | 445 (32.1) | 356 (31.9) |
| Osteoporosis | 317 (12.0) | 266 (19.2) | 346 (31.0) |
| Cancer | 24 (0.91) | 26 (1.9) | 22 (2.0) |
| Hypertension | 516 (19.5) | 371 (26.8) | 358 (32.1) |
| Hearing Loss | 130 (4.9) | 89 (6.4) | 106 (9.5) |
Abbreviations: phenylalanine 508 deletion (F508del), interquartile range (IQR), percent of predicted forced expiratory volume in 1 second (ppFEV1), standard deviation (SD), intravenous (IV), Pulmonary Exacerbation (PEx), cystic fibrosis related diabetes (CFRD), Allergic Bronchial Pulmonary Aspergillosis (ABPA), Non-Tuberculosis Mycobacterium (NTM).
Other includes Native American or Alaska Native; Hawaiian or Pacific Islander; Asian; or Other race categories; counts are combined to comply with CFFPR privacy guidelines.
Insurance categories are not mutually exclusive.
Several patient characteristics were different across all three age groups, with increasing or decreasing prevalence by age (Table 1). Prevalence of full-time employment was highest among younger ages: 53% among people aged 40–49 years old, 46% among those 50–59 years old and 19% among ≥60-year-olds. Interestingly, prevalence of disability did not rise with age, similarly with part-time employment. Rates of positive bacterial cultures decreased with increasing age, with Methicillin-resistant Staphylococcus aureus and Methicillin-susceptible Staphylococcus aureus most prevalent in the youngest age category. Pseudomonas aeruginosa prevalence was highest in 40–49 year olds (51%) compared to 46% for 50–59 year olds and those ≥60 years of age.
The most prevalent complication reported among 40–49 year olds was anxiety or depression (44%) compared to 39% among 50–59 year olds and 35% among ≥60 year olds. With the exception of diabetes (27%), which was lowest in the oldest group, prevalence of CF-related complications such as liver disease, allergic bronchopulmonary aspergillosis, and asthma were generally similar across all age groups. Prevalence of osteopenia was fairly similar across the age groups as well (27% among 40–49 year olds and 32% among ≥60 year olds). Among females, prevalence of osteopenia was 31% and osteoporosis was 20% (all ages). Older age groups had greater prevalence of osteoporosis (31%), hypertension (32%), hearing loss (10%), and arthritis (13%), and there was a trend towards increased reports of cancer. Prevalence of systemic hypertension was higher in males for all age categories, with the highest prevalence at 40.9% of males compared to 25.7% of females among those 60 years or older.
Pancreatic enzyme prescriptions were prescribed to 81% of 40–49 year olds, 72% of 50–59 year olds, and 50% of those age ≥60 years. PwCF aged 40–49 years had the highest proportion of people ever prescribed elexcaftor/tezacaftor/ivacaftor (74%) compared to 66% of those age 50–59 years, and 59% of those age ≥60 years. In contrast, the proportion of 40–49 year olds ever prescribed ivacaftor was half that of those age 60 years and older (3.5% v. 7.4%). Similar proportions of individuals by age group were prescribed dornase alfa (range: 55 to 59%), hypertonic saline (range; 49 to 54%) and inhaled tobramycin (range: 20 to 28%). The distribution of patient characteristics was similar by age group for race, ethnicity, median ppFEV1, nutrition indicators, as well as the proportion reporting having completed recommend screening tests as recommended by CF care guidelines.
There were 914 people ≥40 years of age hospitalized a total of 1,482 times, and 367 people received home intravenous antibiotics. A total of 4,329 (83%) people reported no hospitalizations, 587 (11%) were hospitalized once, and 327 (6%) had ≥2 or more hospitalizations. Most (62%) hospitalizations were pulmonary-related, 12% were GI-related, 6% transplant-related, and 37% had a reason of unknown/other (proportions are not mutually exclusive). People hospitalized ≥2 times were more likely to be female (54% v. 48% among those never hospitalized) and had nearly twice the prevalence of Medicare insurance (55%) compared to individuals with no hospitalizations (30%). Among people hospitalized two or more times in 2022, 102 (31.2%) were individuals post-transplant. Figure 1 visualizes the frequency of hospitalization, showing similar proportions for the three age categories.
Figure 1:
The frequency of hospitalization by age group is presented in Panel A with the frequency of reason for hospitalization summarize in Panel B. In the CFFPR, multiple reasons for hospitalization can be reported and are not mutually exclusive.
Post-transplant individuals accounted for 792 (15%) of the overall study population. Among individuals post-transplant in 2022, the median time since first lung transplant was 10.5 years [IQR 6.0 – 16.5]. In our study, the prevalence of common post-transplant complications was high for diabetes (exceeding 70% in all age categories) and osteoporosis or osteopenia (67%). Prevalence of renal failure requiring dialysis was 4% in 2022 and 2.5% of people >40 years of age with cancer reported as a complication were post-transplant.
Discussion
These results highlight the diverse characteristics of the older CF population. We report characteristics of those ≥60 years of age consistent with other studies that showed later age of CF diagnosis, higher proportion of female sex, and lower prevalence of pancreatic exocrine insufficiency and CFRD. Differences within age groups are consistent with prior studies from over 15 years ago (8–10) suggesting the older CF population is enriched with more individuals with milder phenotypes than younger age groups. Given we show a similar pattern in 2022, we suspect such differences may continue to be attributed to a possible survival advantage as concluded by those earlier studies. To understand the needs of older women with a late CF diagnosis, it is crucial for future research to consider the combined effects of healthcare disparities, caregiving duties, and late diagnosis. The delay in CF diagnosis often compels an acute health event that could have been mitigated with earlier diagnosis and treatment. This perspective could help advocate for increased provider knowledge in adult CF identification, improved national policies, and additional resources for this vulnerable group.
Our findings for adults 40–59 years of age are consistent with a study of PwCF ≥40 years of age in the UK (10) that found a high prevalence of “classic” CF characteristics, and this may represent true aging among those who would not have survived into their forties and beyond in an era of CF care pre-dating the expansion of the adult CF care model and the availability of new therapies such as inhaled antibiotics and CFTR modulator therapy. In our study, adults with CF age 40–59 years old were generally diagnosed as children and have experienced decades of CF therapies and complications, but also have been impacted the most by ETI with greater numbers of eligibility and prescriptions. This is the group that will teach us the most as they age and experience the evolution of classic CF complications complicated by issues of aging (11).
Our analysis also found 15% of older adults with CF are living post-lung transplant, which adds additional complexity to CF care. Even with fewer lung transplants being performed in recent years among PwCF (1), a transplant will still be necessary for some adults and is likely to occur at older and older ages which will add a third dimension of transplant-related health issues. It is possible that post-transplant adults are lost-to-follow-up in the CFFPR if they do not return to their CF center; this may limit generalizability of our data. Linkage of individuals lost to follow-up in the CFFPR with the National Death Index found a higher proportion of deaths among post-transplant individuals (12), so it is also possible many of those lost-to-follow-up are no longer alive. We further acknowledge these data are specific to the United States and may not reflect the experience of older adults with CF in other country settings. Nevertheless, with survival expected to increase (2), providers, researchers, and policy makers alike should consider the unique and diverse care needs of a growing and aging adult CF population (11). With success comes more challenges, and we must be ready to support not only extended duration of life, but quality of life for our CF population.
ACKNOWLEDGMENTS:
The authors would like to thank the Cystic Fibrosis Foundation for the use of CF Foundation Patient Registry data to conduct this study. Additionally, we would like to thank the patients, care providers, and clinic coordinators at CF centers throughout the United States for their contributions to the CF Foundation Patient Registry.
Sources of Support:
This work was funded by the Cystic Fibrosis Foundation.
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