In his adult cystic fibrosis clinic in Denver, Dr. Jerry A. Nick has patients who were not diagnosed until they were 40 years of age or older.
These patients represent the tip of an iceberg of unrecognized patients, and clinicians need to be on the lookout for these individuals, Dr. Nick suggests.
His patients reflect the fact that the clinical presentation of cystic fibrosis can vary along a spectrum of severity. This has become clearer as more and more specific genetic mutations causing cystic fibrosis have been identified.
With that awareness, patients who were once just considered a curious aberration are now recognized as representing something significant, said Dr. Nick, director of the Adult Cystic Fibrosis Clinic of the National Jewish Medical and Research Center.
“These cases have shown up sporadically for years,” he said in an interview.
Dr. Nick recently published a paper on 27 of his late-diagnosis patients (Am. J. Respir. Crit. Care Med. 2005;171:621–6), comparing them with 28 patients diagnosed early who have survived into their 40s. He has also published a review article on long-term survival with cystic fibrosis (Curr. Opin. Pulm. Med. 2005;11:513–8).
Dr. Nick's patients are some of the oldest cystic fibrosis patients yet reported. The median age of his late-diagnosis patients is at present more than 52 years.
They may not be an exclusive group for long, however. Adult diagnosis is already becoming more common, Dr. Nick noted in his article. In 1982, only 3% of patients enrolled in the Cystic Fibrosis Foundation patient registry had been diagnosed after the age of 18 years. By 2002, 10% of the new patients added to the registry that year were diagnosed during adulthood.
Many of the late-diagnosis patients that Dr. Nick described in his article had been seeing physicians for years for recurrent and chronic lung infections, or similar symptoms. They were thought to have asthma, or chronic obstructive pulmonary disease, or something else.
But there is no question about their cystic fibrosis diagnosis, Dr. Nick said. The patients all meet Cystic Fibrosis Foundation diagnostic criteria, and they have had genetic analysis, sweat chloride testing, and/or nasal potential difference testing.
European centers also have begun to take note of late-diagnosis patients, but most of the European patients have been diagnosed in their 20s and 30s.
The importance of Dr. Nick's older patients is that they may help to identify factors associated with long-term survival. The median survival of cystic fibrosis patients is still only 35 years of age, despite improvements in cystic fibrosis treatment.
Dr. Nick has not uncovered any notable clues yet. But there are intriguing, observed differences between the early-diagnosed and late-diagnosed patients. The late-diagnosed patients were less likely to have pancreatic insufficiency, so they tended to have better lung function and nutritional status. They were also less likely to have cystic fibrosis-related diabetes.
One unexpected difference was that 74% of the late-diagnosis patients were women. In the early-diagnosis group, most older patients were male (64%), which is consistent with data in cystic fibrosis patient registries in general, Dr. Nick said. Males also tend to have a longer median survival, by 3–5 years on average.
In addition, a large proportion of the late-diagnosis patients carried nontuberculous mycobacteria. These findings may be the most interesting, Dr. Nick said, as they may indicate something about the airway environment that could be a clue to the patients' long-term survival.
That is also the sole finding so far that might be helpful in identifying the patients who go without a diagnosis for so long. Physicians who see a patient with a nontuberculous mycobacteria infection should have a strong suspicion of cystic fibrosis, he said.
The comparison study found that only 4 of the 27 early-diagnosis patients had at least one positive culture for nontuberculous mycobacteria, whereas 14 of the 28 late-diagnosis patients did. None of the early-diagnosis patients met criteria for an infection, while six of the late-diagnosis patients did.
In contrast, Pseudomonas aeruginosa was found less frequently in cultures from the late-diagnosis patients, although mucoid and nonmucoid strains were still found in more than 50% of cultures.
In general, the late-diagnosis patients had less severe manifestations, but not all of them had mild disease, Dr. Nick noted in the interview. Four of the patients have died. Two required lung transplant. Some had the same genotypes as early-diagnosis patients.