Bronchiectasis (ICD-10: J47) is dilatation (expansion) and destruction of the larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune disorders, and recurrent infections, although some cases appear to be idiopathic. Symptoms are chronic cough and purulent[simptom] sputum – some patients may also have fever and dyspnea. Diagnosis is based on medical history and radiological examinations. Treatment and prevention of acute exacerbations are with antibiotics, drainage of secretions, and management of complications, such as suprainfection and hemoptysis. An important part of treatment is taking care of the underlying disease.
Etiology
Bronchiectasis is most easily viewed as a common ending of various disorders that cause chronic airway inflammation. Bronchiectasis can affect many lung areas (diffuse bronchiectasis) or can occur in only one or two parts (focal bronchiectasis).
Diffuse bronchiectasis most commonly develops in patients with genetic, immune, or anatomical defects that affect the airways. In developed countries, many cases initially appear idiopathic, probably due to a mild and slow onset where the initial trigger cannot be identified until bronchiectasis is recognized.
Cystic fibrosis is the most common cause of diffuse bronchiectasis, and cystic fibrosis is probably responsible for up to 20% of previously idiopathic cases. Even heterozygous patients who typically do not have cystic fibrosis’s clinical manifestations may have an increased risk of bronchiectasis.
Immunodeficiencies such as variable immunodeficiency can also lead to diffuse disease and rare abnormalities of airway structure. It seems that malnutrition and HIV infection also increase the risk.
Congenital mucociliary mucus clearance defects such as primary ciliary dyskinesia may also be the cause, which probably explains some idiopathic cases.
Diffuse bronchiectasis sometimes complicates autoimmune disorders such as rheumatoid arthritis or Sjorgen syndrome.
Allergic bronchopulmonary aspergillosis, hypersensitivity reaction to Aspergillus spp . which frequently occurs in people with asthma, but sometimes also in patients with cystic fibrosis, can cause or contribute to bronchiectasis.
In developing countries, most cases are probably caused by tuberculosis, especially in patients with weakened immune function due to malnutrition and HIV infection.
Focal bronchiectasis typically develops from untreated pneumonia or obstruction (e.g., foreign body obstruction, tumors, postsurgical changes, lymphadenopathy). Mycobacteria (tuberculous or non-tuberculous) can also cause focal bronchiectasis and colonize patients’ lungs with bronchiectasis due to other disorders.
Epidemiology
No data are currently available on the incidence or prevalence of bronchiectasis. The general theory is the emergence of vaccines and antibiotics in the 20. century resulted in a decrease in the incidence of bronchiectasis in developed countries. Available data suggest that the prevalence of bronchiectasis reflects socioeconomic conditions in the population, with a significantly lower prevalence in areas where immunization and antibiotics are available. Bronchiectasis remains a major cause of death in less developed countries, especially in countries with limited healthcare access.
Pathophysiology
The pathophysiology of bronchiectasis is not fully understood, probably because it is part of a common ending of a heterogeneous group of disorders that predispose to chronic airway infection.
Diffuse bronchiectasis appears to begin when the causative disorder triggers inflammation of the small and medium airways, releasing inflammatory mediators from intraluminal neutrophils. Inflammatory mediators destroy elastin, cartilage, and muscles in the larger airways, resulting in irreversible bronchodilation. Simultaneously, in inflamed small and medium-sized airways, macrophages and lymphocytes from an infiltrate that thickens the mucosal walls. This thickening causes airway obstruction, often seen on lung function tests. As the disease progresses, the inflammation spreads beyond the airways, causing fibrosis of the adjacent lung parenchyma. What causes inflammation of the small airways depends on the etiology of bronchiectasis. Factors contributing to inflammation include decreased clearance of mucus from the airway (due to thick, viscous mucus formation in cystic fibrosis, lack of ciliary motility in primary ciliary dyskinesia, or damage to the cilia and/or airways secondary to infection or injury) and decreased host immunity; these factors predispose patients to chronic infections and inflammation. In the case of immune deficiencies, autoimmune inflammation may also contribute.
Focal bronchiectasis
Focal bronchiectasis usually occurs when large airway obstruction occurs. The resulting inability to clear secretions leads to a cycle of infection, inflammation, and damage to the airway wall. The right middle lobe is most commonly affected because its bronchus is small, and its lymph nodes are located close to it. Lymphadenopathy due to non-tuberculous mycobacterial infections sometimes causes bronchial obstruction and focal bronchiectasis.
As inflammation alters airway histology, pathogenic bacteria (sometimes including mycobacteria) colonize the airways. They are frequent colonizers Haemophilus influenza (35%), Pseudomonas aeruginosa (31%), Moraxella catarrhalis (20%), Staphylococcus aureus (14%) I Streptococcus pneumoniae (13%). Colonization of S.aureus is closely related to cystic fibrosis – finding S.aureus undiagnosed cystic fibrosis should be suspected in culture. Also, colonization of P.aeruginosa indicates a more severe disease and predicts faster lung function deterioration. Colonization by multiple microorganisms is common, and antibiotic resistance is of particular concern in patients who require frequent antibiotic therapy during exacerbations.
As the disease progresses, chronic inflammation and hypoxemia cause neovascularization of the bronchial (nonpulmonary) arteries. The walls of the bronchial arteries easily rupture, leading to massive hemoptysis. Other vascular complications include pulmonary hypertension due to vasoconstriction, arteritis, and sometimes shunt from the bronchial to the pulmonary vessels. Colonization by organisms resistant to multiple antibiotics can lead to chronic low-grade airway inflammation. These inflammations may progress to recurrent exacerbations and worsen airflow restriction on pulmonary function tests.
Pathology
Macroscopically, bronchiectasis can be:
- Cylindrical, as mild, uniform airway extensions diffusely distributed in both lungs.
- Secular, with a considerable extension that is spindle-shaped,
- Varicose, irregular appearance due to alternating narrowing and widening.
The bronchi are dilated multiple times and reach the pleura. The lung parenchyma is often atelectatic, grayish-blue, firmly elastic. The bronchial wall may be thickened, and there is a mucous, dense, foul-smelling greenish content in the lumen. The lumen of the dilated bronchi usually contains mucus and purulent exudate. The exudate consists of mucus and neutrophils, and macrophages. The bronchial wall is thickened and diffusely infiltrated by inflammatory cells. The epithelium is hyperplastic and may be metaplastic, multilayered squamous. Chronic inflammatory changes are present in the surrounding lung parenchyma.
Signs and symptoms
Symptoms usually begin quietly and gradually worsen over the years, followed by acute exacerbation episodes. The most common symptom is a chronic cough that spews out vicious, often purulent sputum. Dyspnoea and wheezing are common, and pleuritic chest pain may develop. In advanced cases, dyspnea may be exacerbated by hypoxemia and right heart failure due to pulmonary hypertension. Hemoptysis, which can be massive, occurs due to the airways’ neovascularization.
Acute exacerbations are common and result in new or worsening infections. Exacerbations are characterized by exacerbated cough, increased dyspnea and sputum volume, and purulence. Low-grade fever and constitutional symptoms (e.g., fatigue, malaise) may also be present.
Halitosis (fetor ex ore) and abnormal lung sounds are typical physical examination findings. Batty fingers may be present. In advanced cases, signs of hypoxemia, pulmonary hypertension (e.g., dyspnoea), and right heart failure are common. Rhinosinusitis and nasal polyps may be present, especially in cystic fibrosis patients and primary ciliary dyskinesia. Muscle mass is often reduced, possibly due to inflammation and excess cytokines, and in patients with cystic fibrosis, malabsorption.
Diagnosis
Diagnosis is based on medical history, physical examination, and radiological examinations, beginning with a chest X-ray. Chronic bronchitis can clinically mimic bronchiectasis, but they differ in increased purulence and volume of sputum per day and in dilated airways, which can be seen on radiological images.
A chest X-ray is usually abnormal and can be diagnostic. X-ray findings suggestive of bronchiectasis include thickening of the airway walls and/or their dilation; typical findings include poorly defined linear perihilar densities with the inability to distinguish central pulmonary arteries, poorly visible rings due to thickened airways seen in cross-sections (parallel to X-rays), and “tram strips” caused by thickened, dilated airways perpendicular to RT. Dilated airways filled with mucous plugs can also cause scattered elongated tubular opacities. Radiological samples may vary depending on the underlying disease; bronchiectasis due to cystic fibrosis develops predominantly in the upper lobes, while bronchiectasis due to endobronchial obstruction causes more focal X-ray abnormalities.
High-resolution CT is a test to be chosen to determine the degree of bronchiectasis and is almost 100% sensitive and specific. Typical CT findings include airway dilation (where the inner lumen of two or more airways exceeds the adjacent artery’s diameter) and a seal finger (where a thickened, dilated airway adheres to a smaller artery on the transaxial view). The absence of normal bronchial failure may result in visible medium-sized bronchi extending almost to the pleura. “Tramlines” are easily seen on CT. Airway damage increases over time change progress from cylindrical to varicose and then cystic findings. Atelectasis, consolidation, mucosal plugs, and reduced vascularity are nonspecific findings. In traction bronchiectasis, pulmonary fibrosis pulls or distorts the airways to mimic bronchiectasis on radiological examination.
Lung function tests can help document function and monitor disease progression. Bronchiectasis causes restriction of airflow (reduced forced expiratory volume in one second [FEV 1 ], forced vital capacity[FVC], and FEV 1 / FVC); FEV 1 can be improved with the response to beta-agonist bronchodilators. Measurements of lung volume may be increased or decreased, and carbon monoxide’s diffuse capacity may be reduced.
During the exacerbation-free period, sputum culture should be performed on all patients to determine the predominant colonizing bacteria and their susceptibility. This information helps choose the antibiotics to be used during the exacerbation period. A complete blood count (CC) can help determine the severity of disease activity and identify eosinophilia, indicating complications. Bacterial, mycobacterial cultures ( Mycobacterium avium complex I M.tuberculosis ), and fungal ( Aspergillus spp ) organisms can also help identify the cause of chronic airway inflammation. Clinically significant non-tuberculous mycobacterial infections are diagnosed by finding many colonies of these mycobacteria in cultures from serial sputum samples or in bronchoalveolar lavage fluid in patients with granulomas on biopsy or supporting radiological evidence of the disease.
When the cause of bronchiectasis is not clear, additional tests can be taken to indicate medical history and radiological findings; these tests may be serum immunoglobulins and serum electrophoresis for variable immunosuppression; sweat chloride tests and CFTR gene mutations for cystic fibrosis (and in adults over 40 years of age with no identified cause of bronchiectasis, especially if their upper lobe is affected and they have malabsorption or male infertility); rheumatoid factor, ANA and antineutrophil antibodies for autoimmune conditions; serum IgE and Aspergillus precipitins if patients have eosinophilia; alpha1-antitrypsin for deficiency of the same if CT shows emphysema of the lower lobes.
Primary ciliary dyskinesia should be considered in adults with bronchiectasis who also have chronic sinus disease or otitis media, especially if the problem has existed since childhood. Bronchiectasis in these cases may predominate in the right middle lung lobe and cingulum, and infertility or dextrocardia may be present. Diagnosis requires examining the nasal or bronchial epithelium for abnormal ciliary structures, which requires an electron microscope and is usually done in specialized centers. Nonspecific structural defects can be present in about 10% of healthy people’s cilia and patients with lung disease, and infections can cause transient dyskinesia.
Bronchoscopy is indicated when anatomical or obstructive lesions are suspected.
Prognosis
The prognosis varies. The mean annual decrease in FEV 1 is about 50 to 55 mL (normal reduction in healthy people is about 20 to 30 mL). Patients with cystic fibrosis have the worst prognosis, with a median survival of 36 years, and most patients have intermittent exacerbations.
Treatment
As with all other patients with chronic lung disease, smoking cessation and annual vaccination for influenza and pneumococcal polysaccharides are recommended. Revaccination is recommended again after 5 years in patients under 65 years of age at the time of initial pneumococcal vaccination and for asplenic patients or immunosuppressed patients.
In patients with reversible airway obstruction, bronchodilator therapy (e.g., a combination of a long-acting beta-adrenergic agonist, tiotropium, and a short-acting beta-adrenergic drug, such as those used in patients with COPD) may help improve function and quality of life. Inhaled corticosteroids may also be used in patients with frequent exacerbations or significant fluctuations in pulmonary function measurements.
Patients with cystic fibrosis can be helped by various nebulized treatments, including mucolytic and hypertonic (7%) saline, which reduce the viscosity of sputum and thus improve the clearance of mucus from the airways. There is no evidence that these treatments work in patients without cystic fibrosis, so only moisturizing and saline are prescribed as inhalation treatments. Inhaled terbutaline, mannitol, and mucolytics such as carbocysteine and bromhexine have mechanisms expected to accelerate tracheobronchial clearance. Nevertheless, this approach has non-inclusive results.
There is no consensus on the best use of antibiotics in preventing or limiting the frequency of acute exacerbations. The use of suppressive antibiotics regularly or on a rotational schedule reduces symptoms and exacerbations but may increase the risk of future infections by resistant microbes. Current guidelines suggest using antibiotics in patients with more than 3 exacerbations per year and possibly in those with fewer exacerbations whose culture has been shown to colonize P.aeruginosa. Chronic azithromycin 500mg per os therapy 3 times a week reduces acute exacerbations in patients with or without cystic fibrosis. It is thought that macrolides may benefit due to their anti-inflammatory or immunomodulatory effects. All further therapies depend on the cause.
Acute exacerbations are treated with antibiotics, inhaled bronchodilators, and attempts to improve mucosal clearance (techniques listed above). Inhaled or oral corticosteroids are given to treat airway inflammation. Which antibiotic to use depends on previous culture results and whether the patient has cystic fibrosis or not.
The initial choice of antibiotics for patients with cystic fibrosis depends on previous sputum culture results. During childhood, infections are common S.aureus and H.influenzae, and quinolone antibiotics such as ciprofloxacin and levofloxacin are required. In the later stages of cystic fibrosis, infections may include highly resistant strains of certain gram-negative organisms, including P.aeruginosa. Burkholderia cepacia and Stenotrophomonas maltophilia. In patients with these infections, treatment is with multiple antibiotics (e.g., tobramycin, aztreonam, ticarcillin/clavulanate, ceftazidime, cefaprim). Intravenous administration is often required.
Significant hemoptysis is usually treated by bronchial artery embolization, but surgical resection should be considered if embolization is ineffective and pulmonary function is adequate.
Suprainfection with mycobacterial organisms such as M.avium the complex almost always requires multiple drugs that include clarithromycin 500 mg per or azithromycin 250 mg once daily; rifampin 600 mg once daily or rifabutin 300 mg once daily; and ethambutol 25 mg/kg once daily for 2 months after which 15 mg/kg once daily should be given. Therapy is modified according to cultural results. All medications should be taken until the sputum culture is negative for 12 months.
Surgical resection is rarely required but should be considered when bronchiectasis is localized, therapy is optimized, and symptoms cannot be tolerated. Lung transplantation is also an option in patients with diffuse bronchiectasis. Five-year survival is 65 to 75% with transplantation. Lung function usually improves within 6 months, and improvement persists for at least 5 years.
