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Respiratory clinic - man with COPD, weight loss and a persistent productive cough

Dr Chris Kosmidis, a consultant in infectious diseases, continues our series with a look at an unusual pulmonary presentation in primary care.

The case

A 62-year-old man with COPD presents to his GP with weight loss; he has lost about 8kg over 12 months. He has a persistent productive cough with occasional haemoptysis, profuse night sweats, anorexia and malaise. He has frequent chest infections requiring antibiotics and steroid courses. He is a smoker and was treated for tuberculosis two years earlier and completed the treatment successfully.

Examination reveals severe cachexia, bilateral inspiratory crackles and ankle swelling. Blood tests reveal:

• CRP:  150mg/l.

• Hb: 82g/l.

• Albumin: 27g/l.

A chest X-ray shows a cavity in the left upper lobe and adjacent fibrosis. Due to concern about potential malignancy or recurrence of TB, the patient is referred for a bronchoscopy. Cultures of bronchial lavage grow Aspergillus fumigatus. Aspergillus precipitins are positive at 1:8 and Aspergillus IgG at 78mg/l (normal range <40mg/l). He is started on itraconazole and experiences an improvement in symptoms over several weeks.

The problem

Chronic pulmonary aspergillosis (CPA) is a chronic infection of the lung that affects patients with an underlying lung condition predisposing to cavity formation, such as previously treated TB or atypical mycobacterial disease, COPD, pneumothorax, treated lung cancer (with surgery or radiation therapy), sarcoidosis or bronchiectasis.1 There is usually no underlying immune deficiency. It is an indolent condition, developing over several months. It can, however, progress much faster – within a few weeks – in immunocompromised patients, such as those receiving high doses of steroids.

Worldwide, the most common predisposing condition is previously treated TB. More than a third of people with treated cavitary TB develop positive Aspergillus precipitins, and about one in five develops an aspergilloma.2

Features

CPA presents with respiratory symptoms such as productive cough, haemoptysis, breathlessness, chest pain, as well as systemic symptoms like weight loss, malaise and night sweats. As symptoms present gradually and may be confused with those of an underlying condition like COPD, it may remain unrecognised for years. A CT scan may reveal a thick-walled cavity or cavities, sometimes containing a fungus ball (aspergilloma), and surrounding infiltrates, nodules or fibrosis. There is usually a predilection for the upper lung fields.

Diagnosis

CPA is not suspected initially because of the indolent presentation and non-specific findings. The differential diagnosis usually includes tumour or mycobacterial infection. CPA is diagnosed with a combination of compatible radiological findings and microbiological or serological evidence of Aspergillus. Microbiological evidence consists of growth in culture or a positive molecular diagnostic test – such as a positive PCR or galactomannan – in sputum or bronchoalveolar lavage. Serological evidence is confirmed by positive Aspergillus precipitins of Aspergillus IgG.  

Management

Azoles – itraconazole, voriconazole and posaconazole – are the mainstay of drug treatment. Antifungal medications can offer significant benefit, but this may become apparent only after several months of use, and stopping antifungals may result in recurrence of symptoms.3 As a result, prolonged treatment with antifungals is usually employed, although this may be complicated by side-effects and increased cost. Some of the side-effects may be limiting, such as peripheral neuropathy and liver toxicity with all of the azoles, ankle oedema with itraconazole and a photosensitive rash with voriconazole. Some patients may not respond to oral antifungals or may develop resistance during treatment. In these cases, intravenous antifungals may offer an alternative. Severe haemoptysis may be managed with embolisation, although this may only offer temporary benefit. Surgical management may offer a chance of cure in localised disease.

Management is usually challenging because of the presence of comorbidities such as end-stage pulmonary disease. A multidisciplinary approach with infectious disease and respiratory physicians, surgeons, radiologists, nurse specialists and respiratory physiotherapists is often required. Early recognition and referral to a specialist centre is important, as early antifungal treatment may result in improved quality of life and prevent further deterioration.

 

Dr Chris Kosmidis is an infectious diseases consultant at the University Hospital of South Manchester

 

References

1 Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011;37:865-72

2 Research Committee of the British Tuberculosis Association. Aspergillus in persistent lung cavities after tuberculosis. A report from the Research Committee of the British Tuberculosis Association. Tubercle 1968;49:1-11

3 Koyama K, Ohshima N, Suzuki Jet al. Recurrence of chronic pulmonary aspergillosis after discontinuation of maintenance treatment by antifungal triazoles. J Infect Chemother. 2014;20:375-9.ther. 2014;20:375-9

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