Bronchiectasis, Kartagener Xn

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Diagnosis and reasoning

At first glance, this appears to be a very straightforward case, as this lady has presented with signs and symptoms suggestive of a lower respiratory tract infection. In a typical busy primary care practice, it is all too easy to stop at this point, prescribe antibiotics and send the patient back home. Yet, the examination brings up a couple of unexpected findings - clubbing of all fingers, and even more surprisingly, a right-sided apex beat, indicating that dextrocardia is present ! This illustrates the importance of properly examining all patients. This also casts the history of multiple similar episodes starting from childhood into a totally different light, and allows us to think of two key differential diagnoses. First of all, this might be complex congenital cyanotic heart disease (which can be associated with recurrent respiratory tract infections). It is important to appreciate that cyanotic heart disease does not necessarily need to be associated with overt cyanosis; in addition, note that acyanotic heart disease usually does not give rise to clubbing. The absence of other supportive cardiovascular findings (such as murmurs and thrills) argues against this diagnosis (but does not exclude it). The other major differential diagnosis is Kartagener Syndrome, a rare autosomal recessive disorder associated with recurrent respiratory tract infections and situs inversus. A chest x-ray is a suitable first line investigation; this confirms the presence of dextrocardia and reveals cystic lung shadows suggestive of bronchiectasis. A follow up HRCT (which is the gold standard for diagnosing bronchiectasis) confirms this, and additionally shows that the positions of the thoracic viscera are reversed; an ultrasound scan of the abdomen shows reversal of the abdominal viscera - i.e. this is situs inversus totalis. Thus, this is almost certainly Kartagener syndrome. Note that tests of ciliary function are not essential for the diagnosis of these individuals. An echocardiogram is still important, as Kartagener syndrome can be associated with congenital heart disease; however, in this patient, the heart and great vessels to be structurally normal (except for situs inversus). The acute respiratory tract infection should be aggressively treated with appropriate antibiotics, after sputum cultures are obtained; physiotherapy is essential to aid removal of lung secretions. Pulmonary resection is mainly of value in individuals with focal bronchiectasis; Dornase alfa is of little or no clinical utility in bronchiectasis which is not due to cystic fibrosis. Discussion: Primary ciliary dyskinesia / Kartagener syndrome Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with an incidence of 1 in 15,000 to 1 in 30,000 individuals. It is characterized by chronic upper and lower airway infections, and in 50% of the cases, situs inversus; when the triad of sinusitis, bronchiectasis and situs inversus is present, this is known as Kartagener syndrome. The underlying pathophysiology is a mutation in one or more genes encoding dyneins (a type of motor protein); this results in reduced or absent ciliary function. Note that cilia are found in most tissues of the body - particularly the paranasal sinuses, middle ear, bronchi, epididymis, fallopian tubes and ventricles of the brain. Thus, defective ciliary function at these sites results in the clinical manifestations of PCD. Individuals with PCD can present at almost any age - including from birth to middle age. Clinical features in newborns include continuous rhinorrhea from the first day of life, and respiratory distress or neonatal pneumonia without any obvious predisposing factors. In older children, common presentations include a chronic productive cough, atypical asthma or asthma unresponsive to treatment, rhinosinusitis and chronic and severe secretory otitis media. Symptoms in adults are similar to those in older children; adult females may additionally experience subfertility and ectopic pregnancies, while adult males may have subfertility due to spermatozoa that are immotile or of reduced motility. It is also important to appreciate that PCD can be associated with complex congenital heart diseases, hydrocephalus, polycystic kidney and liver diseases, biliary atresia, or esophageal atresia; this can potentially confound the diagnosis. The most popular screening test is the saccharin test; an abnormal result should be confirmed by examination of cilia by electron microscopy and sometimes with an epithelial cell culture. Note that early diagnosis is key in preventing deterioration of lung function. The respiratory management of these patients includes regular monitoring of lung functions and regular sputum cultures. Airway infections should be treated aggressively and sputum clearance optimized with physiotherapy and exercise. Children should have regular hearing tests as they are at risk for hearing loss. Adults with subfertility may need assisted reproduction techniques.


Discussion

Bronchiectasis is defined as permanent airway dilatation due to repeated airway infection and inflammation. The worldwide prevalence of bronchiectasis is unknown. However, certain demographic groups such as those with poor access to healthcare and individuals with high rates of pulmonary infections in childhood are at an increased risk for development of the condition. Bronchiectasis can manifest as a focal disease involving a lobe or a segment of the lung; or as a diffuse disease process involving both lungs and other extrapulmonary sites including the paranasal sinuses. Note that the dilated airways in bronchiectasis tend to accumulate secretions; this in turn favors microbial colonization and infection, causing further airway destruction and structural derangement, resulting in a vicious cycle. Cystic fibrosis is a well known cause of bronchiectasis; non-cystic fibrosis bronchiectasis (NCFB) typically occurs as a sequelae of infections, congenital conditions (including primary ciliary dyskinesia and alpha 1 antitrypsin deficiency) and immunodeficiencies. Post-tuberculosis bronchiectasis is not uncommon in countries where the disease is prevalent; immune related disorders such as allergic bronchopulmonary aspergillosis (ABPA), connective tissue diseases and inflammatory bowel diseases may also contribute to the development of NCFB. Brochiectasis is also being recognized with increasing frequency in patients with chronic obstructive pulmonary disease (COPD). The clinical features of bronchiectasis are variable; some patients are symptom free and others may have daily symptoms. These include cough, sputum production, chest pain, dyspnea and weight loss. Blood streaked sputum or frank hemoptysis may result from pulmonary exacerbations. The majority of symptomatic patients have an abnormal chest radiograph; specific findings include ring-like shadows and tram line markings. The diagnosis is confirmed by HRCT scanning (which is the current gold standard). The main HRCT findings are airway dilatation and lack of tapering towards the periphery of the lung. Pulmonary function tests typically show modest to severe airflow obstruction. Microbiological examination of sputum is necessary to evaluate for airway colonization and infection. The commonest airway pathogens are Haemophilus influenzae, Pseudomonas spp. and Streptococcus pneumoniae. Note that bronchiectasis is often a manifestation of an underlying condition - where appropriate, further diagnostic workup should be considered. The goals in the management of bronchiectasis are to reduce the number of exacerbations and to improve the quality of life. Specific therapy should be offered to patients with a treatable underlying condition. Patients with acute exacerbations must be treated with antibiotics according to their microbiology results. While maintenance antibiotic therapy is not recommended, it should be noted that macrolides are useful in reducing airway inflammation owing to their anti-inflammatory effect. Bronchodilators such as beta-agonists and anticholinergics, and airway clearance methods (chest physical therapy with postural drainage, mechanical devices etc) are the other modalities of treatment. Resectional surgery may be considered in patients with localized disease who do not respond to conservative management and those with severe hemoptysis that is not controlled with interventional radiology techniques. End stage lung disease in children and adults can be treated with lung transplantation. It is important to note that the rate of decline in lung function is particularly high in patients with chronic colonization with Pseudomonas aeruginosa, a history of severe exacerbations and evidence of systemic inflammation. The prognosis of bronchiectasis varies with the underlying condition. Overall, NCFB has a better prognosis than bronchiectasis associated with cystic fibrosis. The mortality is highest in patients with chronic hypoxemia, hypercapnia, and a large radiographic extent of disease.


Take home messages

  1. A high index of suspicion is important when evaluating patients with recurrent lower respiratory tract infections.
  2. Kartagener Syndrome consists of the triad of sinusitis, bronchiectasis and situs inversus.
  3. Bronchiectasis is often a manifestation of underlying disease; these patients should be further evaluated as necessary.
  4. HRCT is the gold standard for the diagnosis of bronchiectasis.

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  2. Chest. 2008 Oct;134(4):815-23. doi: 10.1378/chest.08-0776: Bronchiectasis: O'Donnell AE.
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