Cystic Fibrosis
GENERAL PRINCIPLES
Definition
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), resulting in dysfunction in numerous exocrine organs.
Epidemiology
• CF is the most common lethal inherited disease affecting the white population.
• The incidence is ∼1 in 3300 white births but all races are affected. The incidence in nonwhite populations is estimated to be 1:9200 Hispanic births, 1:10,900 Native American births, 1:15,000 African American births, and 1:30,000 Asian births. Approximately 1000 new cases are diagnosed annually in the United States and the overall prevalence is just under 30,000 patients.1–3
• Since newborn screening has been adopted by all states the proportion of new cases identified via newborn screening is increasing (62% in 2013).2 Early asymptomatic diagnosis may have better pulmonary function during early childhood.3,4
• Aside from newborn screening most cases are identified in babies born with meconium ileus or young children who present with respiratory symptoms, most commonly recurrent pulmonary infections.
• Up to 10% of patients are diagnosed at age 10 or older.2,5 These patients are more likely to present with nonclassic CF symptoms including bronchiectasis without pancreatic insufficiency, recurrent or chronic pancreatitis, or infertility (azoospermia with congenital absence of the vas deferens).
• The median age of survival in the United States is 40.7 years (95% confidence interval 37.7–44.1).2
Pathophysiology
• CF is a multisystem disease, with highly variable disease presentation.
• Progressive lung disease and chronic respiratory tract infection, however, is the major cause of morbidity and mortality.3
Pulmonary disease is related to abnormal electrolyte transport in airways, resulting in decreased airway surface liquid and impaired mucociliary clearance. Infection, inflammation, and chronic airway obstruction ultimately result in bronchiectasis, chronic infection, and premature death.6,7
Thickened secretions in the pancreatic and biliary ducts result in malabsorption, maldigestion, diabetes, and occasionally liver disease.
• A genetic mutation in the CFTR gene leading to an abnormal protein is the basic molecular defect responsible for CF.
The CFTR gene is located on chromosome 7.
CFTR is a cyclic AMP-regulated chloride ion channel on the apical surface of epithelial cells that primarily plays a role in chloride transport.
In CF, this protein is missing or malfunctioning, leading to abnormal chloride transport.
Abnormal function leads to decreased chloride secretion and increased sodium absorption on the apical surface of epithelial cells. This results in thickened secretions in airways, sinuses, pancreatic ducts, biliary ducts, intestines, sweat ducts, and reproductive tract.6,7
CFTR also plays a role in the regulation of other ion channels that may be important in the pathogenesis of CF.
Many of the specific mechanisms by which the molecular defect of CF leads to clinical disease remain unclear and are the subject of current investigations.
CFTR mutations can be divided into five classes, based on the effect of the mutation on CFTR protein production and function.2
Class I mutations lead to defective protein production. These are often nonsense, frameshift, or splicing mutations leading to complete absence of CFTR protein.
G542X, W1282X, R533X are examples.
Class I accounts for 2–5% of all CF cases.2
Class II mutations lead to defective protein processing. The CFTR protein is produced but is prevented from trafficking properly.
F508del, N1303K are examples.
The most common CFTR mutation is F508del, which is a deletion of three nucleotides which encode phenylalanine (F) at amino acid 508. This mutation is found in over 80% of patients with CF in the United States (46.5% homozygotes and 39.9% heterozygotes).2
Class III mutations lead to defective regulation of the CFTR protein. CFTR is present on the membrane; however, channel activity is diminished. G551D is the most common example.
Class IV mutations lead to defective conduction of the CFTR protein. CFTR is produced, localized, and regulated normally; however, ion conductance and channel opening are reduced. R117H is the most common example.
Class V mutations cause decreased numbers of normally functioning CFTR protein.
Information about specific mutations and reported phenotypes can be found at http://www.cftr2.org. Accessed 27/10/15.
DIAGNOSIS
Clinical Presentation
Pulmonary
• Nearly all patients have chronic sinusitis on radiographic studies. Nasal polyposis is common.
• Chronic lower airway infections are characteristics of this disease.
Chronic infection causes inflammation, increased mucus secretion and obstruction, and direct destruction of pulmonary parenchyma.
Pulmonary infections with Haemophilus influenzae and Staphylococcus aureus are common early in the disease process.
Later, Pseudomonas aeruginosa becomes the dominant lung pathogen in a majority of CF patients. Progressive inflammation, lung damage, decline in lung function, and progressive dyspnea are most closely correlated with this organism.
Infection with other gram-negative organisms such as Burkholderia cepacia can lead to a fulminant course with a high mortality rate.
Colonization with Aspergillus fumigatus is common but invasive disease from this organism is relatively rare.
CF patients are at higher risk for infection with nontuberculous mycobacteria, with prevalence ranging from 4% to 19%. The most common strains identified are Mycobacterium avium complex and Mycobacterium abscessus.8,9
• Acute exacerbation of CF is a common presentation of pulmonary disease.
The typical exacerbation presents with some combination of symptoms, including increased cough, changing sputum, increased shortness of breath, decreased exercise tolerance, and weight loss. Low-grade fever is common but not universal.
The specific factors causing exacerbations are unclear but viral infections have been implicated in some studies.10
Occasionally, a reduction in pulmonary function on spirometry may be the only abnormality noted.
CXRs are often unchanged during exacerbations but are useful to exclude other pulmonary complications of CF.
• Pneumothorax is a relatively common pulmonary complication that presents in CF.
The incidence of pneumothorax rises with increasing age secondary to worsening lung disease. Approximately 3.4% of CF patients will experience pneumothorax (1 in 167 patients per year).11
Patients typically present with chest pain and dyspnea (but may present atypically) because of decreased compliance in the CF lung.
• A second pulmonary complication is minor hemoptysis (<240 mL), which is common (9.1% of patients) and often occurs with acute exacerbations of this disease.12
Approximately 4% of CF patients will experience massive, life-threatening hemoptysis (>500 mL/24 hr) during their lifetime (1 in 115 patients per year).13
Hypertrophic bronchial arteries from chronic inflammation are the typical source of bleeding.
Patients presenting with hemoptysis should be treated with antibiotics.
• Respiratory failure is the most concerning pulmonary presentation of CF. Unless reversible etiologies are responsible, this complication often indicates end-stage lung disease and carries a poor prognosis for recovery.
Gastrointestinal
• Approximately 90% of CF patients exhibit exocrine pancreatic insufficiency.
Patients with pancreatic insufficiency have significantly lower life expectancies than those with pancreatic sufficiency.
Pancreatic sufficiency is more common in patients who present later in life.5
Pancreatic exocrine insufficiency can lead to steatorrhea, chronic malnutrition, edema secondary to hypoalbuminemia, and various vitamin deficiencies.
Fat-soluble vitamins A, D, E, and K are most commonly affected. Vitamin A deficiency can lead to visual deficiencies such as night blindness, and in severe cases xerophthalmia, keratomalacia, and complete blindness. Vitamin D deficiency can lead to poor bone mineralization. Vitamin E deficiency can lead to ataxia and absent deep tendon reflexes.
• Gastroesophageal reflux disease is more common in CF patients than healthy control subjects and is possibly linked to worsening lung disease.14
• Another presentation of GI disease is the distal intestinal obstruction syndrome (DIOS), which can be considered an adult equivalent of meconium ileus.
Colicky abdominal pain with a palpable mass is a typical presentation.
Radiographic patterns consistent with partial or complete obstruction can be seen on obstructive series.
Caution must be exercised, however, because these signs and symptoms are present in other abdominal conditions that present in CF patients. Empiric treatment of DIOS while evaluation is underway for other conditions is recommended.
• Volvulus, intussusception, and rectal prolapse can occur.
• Cholelithiasis and cholecystitis are seen.
• CF can be associated with an asymptomatic increase in alkaline phosphatase and a mild transaminitis in up to one-third of patients, whereas biliary cirrhosis is much less common.
• A small percentage of patients do have significant liver disease with about 3% of deaths in CF patients attributed to liver disease.2
Endocrine and Reproductive
• Men are usually infertile secondary to obstructive azoospermia. Patients that are diagnosed at older ages may present with congenital absence of the vas deferens.
• Women have reduced fertility because of thick cervical mucus as well as other, less understood factors.
• Puberty is often late in onset owing to malnutrition.
• Osteoporosis occurs in approximately one-third of adult CF patients.
• Diabetes mellitus is common in CF, affecting more than 20% of adults.2
Diabetes in CF is primarily due to deficient insulin production, although insulin resistance may play a role as well.
CF patients may be dependent on insulin for glucose control but diabetic ketoacidosis is rare.
Diagnostic Criteria
• The diagnosis of CF is based on clinical presentation coupled with confirmatory testing.
• At least one criterion from each set of features is required to diagnose CF15:
Compatible clinical feature of CF (persistent colonization/infection with typical organisms, chronic cough and sputum production, persistent CXR abnormalities, airway obstruction, sinus abnormalities/polyps, clubbing, meconium ileus, DIOS, rectal prolapse, pancreatic insufficiency/pancreatitis, jaundice/biliary cirrhosis, malnutrition, acute salt depletion, chronic metabolic alkalosis, obstructive azoospermia) OR
Positive family history OR
Positive newborn screening test
AND
Elevated sweat chloride >60 mmol/L on two occasions OR
Presence of two disease-causing mutations in CFTR OR
Abnormal nasal transepithelial potential difference test
Differential Diagnosis
• Primary ciliary dyskinesia: bronchiectasis, sinusitis, and infertility are common. Gastrointestinal (GI) symptoms are limited and sweat chloride levels are normal. Dextrocardia or situs inversus totalis can be seen.
• Shwachman–Diamond syndrome: pancreatic insufficiency, cyclic neutropenia, and short stature are seen. Sweat chloride levels are normal.
• Young syndrome: bronchiectasis, sinusitis, and azoospermia. Respiratory symptoms are mild, and there is a lack of GI symptoms. Sweat chloride testing is normal.
• Immunoglobulin deficiency leads to recurrent sinus and pulmonary infections and can cause bronchiectasis. GI symptoms are absent and sweat chloride testing is normal.
• Idiopathic bronchiectasis.
• Chronic rhinosinusitis.
• Chronic idiopathic pancreatitis.
Diagnostic Testing
• Diagnosis of CF is usually made during childhood. Approximately 10% of patients are diagnosed after age 10.5 In 2013, over 60% of new diagnoses were made from newborn screening, which has increased the frequency of early diagnosis.2
• Pilocarpine iontophoresis, or sweat testing, is the most common confirmatory test and is the gold standard for CF diagnosis.15
A quantitative test with a chloride value of >60 mmol/L on two occasions is consistent with CF.
Other conditions produce abnormal sweat tests but can usually be differentiated from CF based on their clinical presentation.
Borderline or nondiagnostic results should prompt repeat or additional testing depending on clinical suspicion.
• Transepithelial potential difference can be used as confirmatory testing in the rare instance in which CF is suspected clinically but sweat testing is inconclusive. This testing is only available at specialized centers, and should be repeated on two separate days. Voltage across epithelial lining of the nose is measured at rest, after sodium channel inhibition, and after CFTR stimulation.
• Genetic testing for CF is available but usually is not used as the initial diagnostic test. There are >1800 known mutations and a number of unknown mutations that can lead to CF disease.
Two mutations on different alleles must be present to diagnose CF.
Commercially available probes, while identifying >90% of abnormal genes in the white Northern European population, test for a minority of known CF mutations.
Full gene sequencing is available but interpretation may be complex.
• Other diagnostic evaluation can support the presence of CF but is generally neither specific nor sensitive for the diagnosis.
• Pulmonary function tests show an obstructive pattern early in the disease and tend to change to a mixed obstructive and restrictive pattern later when more fibrosis is present.
• Early in the disease, radiographic testing tends to show hyperinflated lungs. Bronchiectasis with cyst formation and mucus plugging is a later finding.
• Sputum cultures are typically positive for multiple organisms, including P. aeruginosa,S. aureus, nontypeable H. influenzae, Stenotrophomonas maltophilia, B. cepacia, and mucoid variants of P. aeruginosa. Use of special culture media to identify fastidious organisms is recommended. Nontuberculous mycobacteria are frequently isolated and may be pathogenic.8,9
• Testing for pancreatic insufficiency and malabsorption is not commonly done, as the diagnosis based on history, vitamin deficiency, and response to pancreatic enzyme supplementation is often sufficient for diagnosis. Seventy-two-hour stool collections for fecal fat or measurement of fecal elastase levels can be helpful in situations where the diagnosis is not clear.
TREATMENT
• The overall goals of CF therapy are to improve quality of life, decrease number and frequency of exacerbations and hospitalizations, reduce the rate of decline in lung function, and prolong life expectancy.
• Comprehensive care at an accredited CF care center is recommended.
Pulmonary
• Management of the acute pulmonary exacerbation is probably the most common reason for the hospital admission of CF patients.
• Immunizations should be kept up to date in an attempt to prevent exacerbations. Yearly influenza vaccination decreases the frequency of infection.2
• Pulmonary rehabilitation, when performed with exercise rehabilitation may improve functional status and assist with airway clearance.16–18
• Inhaled bronchodilators (e.g., albuterol, salmeterol, formoterol) are recommended for all CF patients, particularly in association with chest physiotherapy or other nebulized agents. Bronchodilators facilitate clearance of airway secretions and limit bronchial constriction seen in response to certain inhaled agents, such as hypertonic saline and dornase ALFA.
• Respiratory therapy, including chest percussion and postural drainage, has long been known to be efficacious in exacerbations.19,20 Other techniques including percussors, pneumatic compression vests, and oscillating positive expiratory pressure devices such as the Flutter and Acapella are available to assist in airway clearance.21–25
• Hypertonic saline (7%) is administered as an inhalation, and functions to improve mucociliary clearance of airway secretions.26
Hypertonic saline increases water content of secretions by creating a high osmotic gradient.
Mucus clearance is improved, with mild improvements in lung function and decreased incidence of respiratory exacerbations.
Albuterol should be administered prior to hypertonic saline to reduce bronchospasm. Patients with FEV1 <40% should be given a test dose under observation before initiating therapy at home.
• Inhaled recombinant DNase (dornase ALFA) digests extracellular DNA and reduces the viscosity of CF sputum.27,28
Shown to be effective in reducing sputum viscosity and improving pulmonary function.
In patients with normal pulmonary function, dornase ALFA has been shown to slow the rate of decline in lung function.
Dornase ALFA decreases the incidence of respiratory tract infections requiring parenteral antibiotics.
Side effects include pharyngitis, laryngitis, rash, chest pain, and conjunctivitis.
• Antibiotics are the main treatment for acute exacerbations.29
Antibiotic use in CF patients differs from that in other patients. Higher doses of antibiotics are needed because of increased clearance and volumes of distribution. Longer courses of antibiotics are required. Fourteen- to twenty-one-day courses are typical of effective regimens.
Sputum culture results should guide antibiotic choice.
In general, antibiotics are selected based on respiratory tract cultures and susceptibilities, however:
The utility of in vitro susceptibility testing has been questioned, since there appears to be discordance between susceptibility testing and clinical response to antibiotics.
In a study published in 2003, treatment outcomes of patients experiencing a CF exacerbation with IV tobramycin or IV ceftazidime did not correlate with MIC values of P. aeruginosa obtained from sputum cultures.30
Oral antibiotics are appropriate for mild exacerbations. The main barrier to using oral antibiotics is the limited number of agents active against Pseudomonas. Ciprofloxacin (750 mg PO bid) is the antibiotic of choice against Pseudomonas. Use of this drug should be limited to 3-week courses given the rapid rise of resistant organisms when longer courses are used.
For moderate to severe exacerbations or failed oral treatment courses, IV regimens are the standard of care.29
A typical two-drug regimen consists of an aminoglycoside (gentamicin/tobramycin,3 mg/kg IV q8h or 10 mg/kg q24h following peak and trough levels) plus an extended-spectrum penicillin (piperacillin/tazobactam, 4.5 g IV q6h) or cephalosporin (cefepime, 2 g IV q8h).
Measurement of aminoglycoside peaks and troughs or other evaluations of aminoglycoside pharmacokinetics should be employed to optimize aminoglycoside dosing and prevent toxicity. Once-daily dosing is preferred.
Occasionally, methicillin-resistant S. aureus is isolated from the sputum and requires IV vancomycin (15 mg/kg adjusted to maintain a trough of ∼10–15) for adequate coverage.
Inhaled tobramycin in patients with chronic airways infection with P. aeruginosa used in 28-day cycles was shown to improve pulmonary function and decrease the rate of hospitalization.31
Inhaled aztreonam in patients with chronic airways infection with P. aeruginosa has been shown to improve pulmonary function and increase the time until subsequent antibiotic treatment.32,33
There is some evidence that home IV treatment can be as effective as hospital treatment.29,34,35 However, the decision of inpatient versus outpatient treatment must be made on an individual basis. Resources available in the hospital such as intensive monitoring and extensive chest physical therapy are generally unavailable at home.
• Inflammation in CF is an additional target for CF therapeutics.
Chronic treatment with azithromycin (500 mg three times a week) in patients chronically infected with P. aeruginosa has been shown to improve lung function and reduce days in the hospital for treatment of acute exacerbations.36 Its use should be limited to patients with multiple cultures negative for nontuberculous mycobacterial infection.
One trial compared prednisone therapy 1 mg/kg versus 2 mg/kg versus placebo on alternate days. The prednisone group had a higher percentage of predicted forced vital capacity.37 However, complications of steroid therapy, such as growth retardation and glycemic control, have limited the use of this therapy, and long-term use should be avoided.
High-dose ibuprofen has been used with some success in young patients with mild disease but is again limited by side effects including renal failure and peptic ulcer disease.38,39
• Treatment for chronic respiratory failure is usually supportive.
Oxygen therapy should be provided based on standard rest and exercise oxygen assessments.
Noninvasive ventilation or even intubation has been used as a bridge to lung transplantation.
Bilateral lung transplantation is the treatment of choice.40 The challenges of lung transplantation for this population are formidable given the incidence of pre-existing infections and poor nutrition. However, success rates compare favorably to other indications for transplantation.
• Chronic sinusitis is common, and many patients benefit from nasal steroids. Nasal saline washes are helpful. Some patients may require functional endoscopic sinus surgery and nasal polypectomy.
Gastrointestinal
• Achieving adequate nutrition in CF patients affects both pulmonary status and overall mortality.
Replacement of pancreatic enzymes as supplements is important for this goal.41
The usual starting dose is 500 lipase units/kg/meal PO, which can be increased to maximum dose of 2500 units/kg/meal. Dosing is adjusted to achieve one to two semisolid stools per day and maintain adequate nutrition.
Acid suppression may be necessary in some patients as enzymes may be inactivated in an acidic environment, though supporting data are limited.42
Adequate proportions of fat and protein calories need to be ingested, which usually require increased caloric intake.
Dietary goals should aim for a body mass index of ≥50th percentile or in adult males ≥22 and females ≥23. Better lung function is associated with a higher BMI. More severe disease and worse pancreatic function result in greater caloric deficits and intake recommendations should be tailored to the individual patient. Nutritional supplementation should be provided when appropriate.2,41
Fat-soluble vitamins should be provided in supplements.
• The preferred treatments for other GI complications are less clear.
Ursodeoxycholic acid probably has a role in the management of CF-induced cholestasis.
Management of end-stage liver disease and the resulting complications of portal hypertension are the same as in other etiologies of end-stage liver disease.
DIOS may be managed by oral administration of laxative electrolyte solutions such as magnesium citrate or polyethylene glycol. With the presence of complete obstruction, diatrizoate meglumine and diatrizoate sodium (hypaque) enemas can be used as both a diagnostic and a therapeutic maneuver.43 Surgery is rarely required.
Endocrine and Reproductive
• Glucose intolerance as well as diabetes mellitus is more common in CF patients. Screening with a 2-hour 75-g glucose tolerance test should be done yearly.44 Management of CF-related diabetes mellitus generally relies on insulin therapy.
• Osteopenia should be managed with calcium and vitamin D supplementation. Bisphosphonate therapy is effective for osteoporosis in adult CF patients.45
• Most males are infertile secondary to obstructive azoospermia. Microsurgical epididymal sperm aspiration with intracytoplasmic sperm injection into the ova may be used to overcome male infertility. Likewise, intrauterine insemination has overcome many of the factors that decrease fertility rates for female CF patients.
Lung Transplantation
• CF remains one of the most common indications for bilateral lung transplantation.
• In general, transplantation improves life expectancy in patients who have an estimated 5-year survival of 30% or less.40
• Criteria for referral to a lung transplantation center include46,47:
FEV1 <30% predicted or a rapid decline in FEV1 or 6-minute walk distance <400 m. Other criteria should be met in addition to a decline in FEV1 prior to referral to a lung transplantation center.
Increasing frequency of exacerbations.
Refractory/recurrent pneumothorax.
Recurrent hemoptysis.
Hypoxemia or hypercapnia.
Pulmonary hypertension.
• Many transplant centers consider respiratory tract infection with B. cepacia complex to be a contraindication for lung transplantation in CF patients.
Emerging Therapies
• Aggressive treatment of pulmonary infections and inflammation, as well as attention to the nutritional issues, involved in CF has largely been responsible for the significant improvement in mortality over the past five decades.
• New understanding of the genetic and molecular basis of CF holds the promise for similar advances in the decades ahead.
• New therapies can be divided into those that attempt to improve the function of the mutant CFTR protein, manipulate the function of alternative ion channels, and those that attempt to treat the genetic defect directly.
• Since the isolation of the CF gene in 1989, there has been interest in applying the principles of gene therapy to CF. The theoretical promise of this approach is still great but there are many technical difficulties to overcome before this becomes a common approach to CF therapy.
• CFTR modulators
Ivacaftor (150 mg PO bid), which was approved by the U.S. Food and Drug Administration (FDA) for use in CF in January 2012, is the first agent that restores function by activating mutant CFTR.48
Approved for use in patients with the G551D mutation who are >6 years old, which is present in ∼5% of patients with CF and causes a class III mutation.
Developed using large-scale chemical screen for agents that increase chloride ion efflux in cells expressing a G551D CFTR mutant.
A phase III randomized, placebo-controlled trial demonstrated an increase in FEV1 by 10.4% with ivacaftor compared to an FEV1 decline of 0.2% in placebo controls after 24 weeks of treatment. Sweat chloride levels, frequency of CF exacerbations, and adverse events were all significantly lower in patients treated with ivacaftor. Weight gain was common in subjects receiving ivacaftor.
Ivacaftor is best absorbed when combined with fat- and enzyme-containing meals, and the channel modulating effects may decrease rapidly with missed doses. Reinforcement of proper use is crucial for optimal outcomes.
Ataluren (PTC124) is an agent that causes ribosomes to read through premature stop codons, without affecting their ability to recognize normal stop codons. Early clinical trials have shown significant improvements in nasal potential differences in children, but a phase 3 clinical trial has not definitively substantiated its efficacy.49,50
Oral agents intended to correct the abnormal CFTR trafficking that characterizes the F508del mutation are in various phases of preclinical and clinical development. These agents may be administered with ivacaftor in an attempt to increase their efficacy.51
SPECIAL CONSIDERATIONS
• Corresponding with the increasing life expectancy are increasing rates of pregnancy in CF patients.
• Women with good lung function and good nutritional status generally do well during pregnancy.52,53
Prepregnancy FEV1 <50% of predicted is associated with poorer outcomes. For example, in a UK study by Edenborough, women with FEV1 <60% delivered more preterm infants and had a greater decrease in lung function during the pregnancy compared to those with milder disease.54
Women should be encouraged to reach 90% of their ideal weight before their pregnancy. Nocturnal tube feeds can be used in those patients having difficulty gaining weight.
Exacerbations should be treated aggressively. Cephalosporins and synthetic penicillins are generally safe. Aminoglycosides potentially cause fetal ototoxicity but may be necessary.
• Families should be counseled on the genetic risk of CF. All children of a parent with CF carry a single CF mutation; their chances of having CF disease depend on the genetics of the affected parent’s partner.
COMPLICATIONS
• Pneumothorax is an indication for hospital admission.55
If small (<20% of the hemithorax volume), pneumothoraces can be managed conservatively with serial CXRs.
BiPAP treatment should be withheld until the pneumothorax has resolved. Airplane travel, weight lifting, and spirometry should be avoided for 2 weeks after the pneumothorax has resolved.
In general, airway clearance measures utilizing positive expiratory pressure (flutter valve), intrapulmonary percussive ventilation, and exercise should be avoided in most instances of large pneumothorax.
If the pneumothorax enlarges or is symptomatic, a chest tube should be placed.
Obliterative procedures such as pleurodesis should be considered for persistent and recurrent pneumothoraces.
Surgical pleurodesis is preferred over chemical pleurodesis.
• Hemoptysis is usually minor and responds to conservative treatment with IV antibiotics.55
Moderate to massive hemoptysis usually requires a more interventional approach.
Basic treatment involves correction of coagulation parameters, withholding chest physiotherapy, and stopping inhaled antibiotics.
Bronchial artery embolization plays an important role in massive or recurrent hemoptysis. A small study showed decreased bleeding and pulmonary exacerbations as well as increased quality of life when early bronchial artery embolization was used.56 Bronchoscopy is not recommended prior to bronchial artery embolization.
Repeated embolization in the setting of recurrent hemoptysis is frequently successful, and atypical sources of neovascularization should be considered in patients with prior embolization and persistent bleeding.
Surgery is the last option if bronchial artery embolization fails to control the bleeding.
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