What are Signs and Symptoms of Cystic Fibrosis?
Cystic fibrosis is a progressive disease that involves a number of different organs. Therefore, people with cystic fibrosis can have a variety of symptoms, depending on their age and the severity of their disease. The severity of disease is largely determined by the specific CFTR mutations. But severity of disease is also related to the type of infections that are present in the airway, as well as several “modifier” genes, which in some cases appears to alter the expected clinical features. More than 75 percent of people are diagnosed with cystic fibrosis by age 1, most by state-run newborn screening programs. However, in people with less severe symptoms born before widespread implementation of newborn screening, the diagnosis may be delayed for decades.
Other Respiratory Complications
Many people with cystic fibrosis have a degree of airway bronchospasm that resembles asthma. In these people, respiratory symptoms and lung function (Forced Expiratory Volume 1 second or FEV1) are improved through the use of bronchodilators. Peoples with more advanced lung disease are at risk for complications such as bleeding into the airways (hemoptysis). Coughing up blood is a common feature of increased infection and usually is resolved with antibiotics. More severe complications include collapse of lobes or leaking of air outside of the lungs (pneumothorax). These complications are associated with advanced lung disease and can be a cause of sudden worsening of respiratory symptoms. Urgent medical evaluation and treatment are required.
Pulmonary Exacerbation of CF
Like other lung diseases, such as asthma and emphysema, one of the most important features of cystic fibrosis is episodic exacerbation in disease severity. Most people with CF will have less than one exacerbation per year, but with advancing lung disease, the frequency of exacerbations typically increases. Clinical features include increased cough, shortness of breath, sputum production, fatigue, decreased appetite and weight loss. No definitive diagnostic criteria exist, although usually several of these signs and symptoms will be present.
Like the bronchi, the small ducts of the pancreas can become obstructed and damaged by thick secretions. Nearly 90 percent of people with CF lack the capacity to excrete sufficient pancreatic enzymes or bicarbonate into the duodenum (pancreatic insufficiency). The duodenum is the first portion of the small intestine. This condition greatly reduces the capacity to metabolize and absorb dietary fats and proteins. Carbohydrate absorption can also be impaired. Symptoms include greasy and foul-smelling diarrhea with intermittent constipation, abdominal pain, failure to gain weight and malnutrition. Historically, children with CF died in early childhood as a result of pancreatic insufficiency, before the lung manifestation of the lung disease became severe. Development of pancreatic replacement enzymes and other nutritional supplements have significantly reduced the complications associated with pancreatic insufficiency.
Insulin is produced by cells of the islets of Langerhans, located within the pancreas. Even with pancreatic insufficiency, most children with CF are still capable of producing sufficient insulin. However, in adulthood, increasing numbers of men and women with CF will require supplemental insulin, as the residual islet cell function declines. CF-related diabetes (CFRD) includes signs and symptoms from Type I and Type II diabetes that are encountered in the general population. Often the symptoms of CFRD are quite subtle, and can include weight loss or inability to regain weight after an exacerbation, as well as unexpectedly rapid decline in lung function. Administration of insulin is nearly always associated with improved weight gain and lung function.
As with the lungs and pancreatic ducts, the mucus of the bowel is abnormal in CF patients. At birth, up to 20 percent of CF patients will have an obstruction of the bowel, termed “meconium ileus.” Many people with CF experience difficulty with constipation throughout life. In the most extreme form, people with cystic fibrosis can become severely obstructed with stool. This condition is termed the Distal Intestinal Obstruction Syndrome (DIOS), and requires prompt and aggressive treatment by doctors familiar with the condition.
Inflammation and infection of the upper airways and sinuses are extremely common in people with cystic fibrosis. Symptoms include runny nose, recurrent or chronic sinusitis, postnasal drip or nasal polyps. Aggressive medical treatment of CF sinus disease is very important, as poorly controlled sinusitis can greatly worsen the severity of CF lung disease and have an impact on quality of life. Although sinus surgery is sometimes needed, this should only be performed by an Ear Nose and Throat (ENT) specialist experienced in the treatment of CF-related sinus disease.
Fertility and Cystic Fibrosis
Over 98 percent of men with cystic fibrosis are infertile. Semen analysis demonstrates the absence of sperm (azoospermia) due to damage to the vas deferens duct, which occurs prior to birth. This results in a condition termed congenital bilateral absence of the vas deferens (CBAVD). However, when the obstruction is bypassed by directly aspirating the sperm from the epididymis, the sperm are generally found to be normal. Thus, for men with cystic fibrosis who wish to father children, various techniques are available to harvest sperm, which can then be used for assisted reproduction.
The first report of a successful pregnancy by a woman with cystic fibrosis appeared in 1960. Historically, women with CF were considered to have decreased fertility, usually attributed to dehydrated and thickened cervical mucus. However, women with CF generally have normal reproductive anatomy, and pregnancies followed by uncomplicated deliveries are common. While a number of aspects of the female reproductive system can be altered by CF, the decreased fertility rate previously observed in women was probably related more to malnutrition, delayed menarche (the first menstrual period), overall poor health and a shortened life span. All women with cystic fibrosis should be considered capable of childbirth, and appropriate birth control should be considered to prevent unplanned pregnancies. Many CF-related treatments, including certain classes of antibiotics, are not recommended during pregnancy, or have unknown consequences. Thus pregnancy testing should be considered before initiating treatment with such medications.
With the steady increase in the life expectancy of people with cystic fibrosis, many women with CF are considering planned pregnancies. Each situation is different, and sweeping recommendations are not possible. The non-CF partner should undergo genetic testing to determine if he is a CF carrier. Typically, CF pregnancies are considered “high risk.” Common issues include difficulty in achieving recommended weight gain (especially in women who are undernourished prior to pregnancy), high rates of gestational diabetes, pulmonary exacerbations, high rates of C-sections and low birth weights.
Despite these risks, women with cystic fibrosis generally have done well during the actual pregnancy and childbirth. The greatest concern often lies with the capacity of the mother to maintain her demanding treatment regimen in the setting of the demands of raising a child. Clearly, the severity of the mother’s lung disease, the presence of other CF-related conditions such as diabetes and the amount of support present from spouse and family are important factors in this decision. Couples need to have a realistic understanding that the progression of CF is difficult to predict, and a mother may not survive to see her child reach adulthood. These considerations are also present when men with CF consider having children, or when men or women with CF consider adoption. Finally, each child conceived from a parent with CF will be a CF carrier, and has a 50 percent chance of having CF if the other parent is a carrier. Some people with cystic fibrosis choose not to have children to avoid passing the gene onto future generations.
CF Diagnosed in Adulthood
With over 1,800 different CFTR
mutations described, it is now recognized that many of the less common mutations allow for partial function of the gene and protein, and a less severe form of disease. Increasingly, it is evident that “mild” forms of CF remain undiagnosed until adulthood. Usually, people with cystic fibrosis diagnosed in adulthood will have normal pancreatic function. In the most extreme form, non-classic cystic fibrosis can appear to present with involvement of a single organ, such as recurrent pancreatitis or male infertility due to CBAVD. However, doctors should be cautioned against assuming that people with mild CF mutations and limited organ involvement will never face the respiratory difficulties common to classic cystic fibrosis. Careful analysis of these people has often demonstrated signs of early CF lung disease. In many cases, typical and severe CF lung disease can develop, albeit decades later in life than in people with the classic form of CF. While the clinical course of peoples diagnosed as adults with nonclassic CF is still under investigation, it is apparent that life expectancy is significantly longer than for people diagnosed in childhood. It has been shown that people diagnosed later in life respond well to standard CF care.