Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein.^1–4 This protein, which is located in the epithelial cell membrane, functions normally as a cAMP-activated chloride channel, transporting chloride, and passively water, out of the cell into the adjacent lumen.^3,4 CFTR also plays a role in bicarbonate transport from the cell into the lumen. CFTR is involved in regulating sodium channels for airway epithelial cells, helping to limit sodium and water reabsorption from the lumen to the cells. In sweat gland ductal cells, CFTR is responsible for transport of chloride into the cell, leading to increased salt in sweat when CFTR is defective. These mechanisms help explain the clinical manifestations of the disease.

The CFTR gene is located on the long arm of chromosome 7. The most common mutation that causes CF is F508 deletion. There are more than 1500 less-common mutations grouped into six classes.^1,5,6

The sinuses, lungs, pancreas, liver, biliary tract, gastrointestinal tract, and reproductive system express the CFTR gene and are affected by its mutation.^2–4 However, the relationship between genotype and clinical manifestations is not always consistent. The most important pathophysiologic consequence of these CFTR defects is diminished water in mucus and most exocrine secretions along with associated electrolyte and other abnormalities.⁴ Mucus and exocrine secretions are more viscid, and they are difficult to clear, causing airway and ductal obstruction.^3,7 In the airways, these mucus and possibly other abnormalities predispose to chronic inflammation as well as chronic infection with a characteristic group of bacterial organisms including Pseudomonas aeruginosa, Aspergillus, and Staphylococcus aureus.^2,4 This predisposition to specific infections has yet to be fully elucidated. Various hypotheses have been proposed (Table 39-1).^3,4

Pancreatic exocrine insufficiency resulting in GI malabsorption and malnutrition is a consequence of qualitative and quantitative abnormalities of pancreatic secretions reaching the GI tract. Pancreatic endocrine insufficiency, resulting in diabetes mellitus, or acute pancreatitis may ensue eventually, due to pancreatic auto-digestion by stagnant activated enzymes.^4,7 Abnormal intestinal mucus and biliary secretions also play roles in the malabsorption and various GI and hepatobiliary obstructive sequelae found in CF.⁷

Patients with CF often have elevated sweat chloride and sodium concentrations because of defective chloride transport by the sweat gland duct cells.¹

Early diagnosis has been shown to lead to improved outcomes, including decreased morbidity and delayed mortality.⁸

In this era of routine newborn screening, it is unlikely that undiagnosed, untreated CF patients will present to the ED. Historically, failure to thrive with a history of chronic GI or respiratory problems was a typical presentation.⁷ CF should be considered in any patient with chronic diarrhea, recurrent respiratory infections, or atypical asthma.⁹ Hypoproteinemia and edema may develop in those with prominent malabsorption.¹⁰ Malabsorption can lead to vitamin deficiencies, particularly of fat-soluble vitamins. Hemorrhage due to vitamin K deficiency as well as neurologic abnormalities and hemolytic anemia from vitamin E deficiency have been described.^10,11 Patients with clinical findings suggestive of CF should be referred for diagnostic evaluation.

PULMONARY COMPLICATIONS

Known CF patients can present to the ED with various acute complications, and the most common is a pulmonary exacerbation manifested by an increase of respiratory symptoms. Pulmonary exacerbations are often due to acute airway infections triggered by common respiratory viruses. The youngest patients with CF have infections caused by S. aureus or Haemophilus influenzae. Eventually, however, Pseudomonas aeruginosa becomes the most prevalent organism.^12,13 In chronically infected CF patients, P. aeruginosa tends to mutate, becoming more mucoid, less motile, and very difficult to eradicate with antimicrobial therapy.^12,13 Burkholderia (formerly Pseudomonas) cepacia is a particularly virulent organism in patients with CF.^4,11 Nontuberculous mycobacterial infections can occur and are difficult to eradicate.¹¹ Methicillin-resistant S. aureus (MRSA) is an important pathogen in the respiratory tracts of patients with CF. Because MRSA infections have been associated with a higher risk of mortality, they should be treated aggressively.¹⁴

Chronic infection and inflammation, along with repeated exacerbations, result in destruction of the airway.^4,11,15 Bronchiolitis-like manifestations may develop initially, accompanied by bronchitis later. With prolonged disease, bronchiolar obliteration, bronchiolectasis, and bronchiectasis ensue.^4,11 Mucus plugging and airway obstruction are prominent features of CF, leading to atelectasis, enlarged air spaces, and ventilation perfusion mismatching.

Pneumothorax, sometimes a tension pneumothorax, may result from the rupture of an emphysematous bulla or bleb, and must be excluded in any patient with CF who deteriorates suddenly.^10,11 It is not unusual in older teenagers and adults, or in patients with significant impairment in lung function, and can often recur.^11,16,17 Pneumothorax is a poor prognostic indicator and is associated with a subsequent increase of hospitalizations, hospital days, and 2-year mortality.¹⁶

Patients with CF may have hemoptysis, particularly during exacerbations. Bleeding is usually minor and not dangerous. Massive hemoptysis, >240 mL/day or >100 mL/day over several days, can cause life-threatening asphyxia or hypotension.¹⁷ It is thought to result from persistent airway inflammation and erosion into markedly enlarged bronchial arteries.¹⁷ Like pneumothorax, massive hemoptysis is more prevalent in older patients and in those with more severe pulmonary impairment. S. aureus in sputum cultures is also associated with an increased risk. Massive hemoptysis is a poor prognostic indicator, similar to pneumothorax.¹⁷