BMJ Open Resp Res: first published as 10.1136/bmjresp-2016-000155 on 16 December 2016. Downloaded from Respiratory infection Clinical manifestations and outcomes of pulmonary aspergillosis: experience from Pakistan Nousheen Iqbal,1 Muhammad Irfan,1 Ali Bin Sarwar Zubairi,1 Kauser Jabeen,2 Safia Awan,3 Javaid A Khan1 To cite: Iqbal N, Irfan M, ABSTRACT KEY MESSAGES Zubairi ABS, et al. Clinical Introduction: Pulmonary aspergillosis has variable manifestations and outcomes course of illness, severity and outcomes depending on of pulmonary aspergillosis: ▸ Pulmonary aspergillosis has variable clinical pre- underlying conditions. There is limited data available experience from Pakistan. sentations and outcomes. BMJ Open Resp Res 2016;3: on the clinical manifestations and outcome of ▸ Very limited data is available from Pakistan on e000155. doi:10.1136/ pulmonary aspergillosis from Pakistan. its different clinical presentations. bmjresp-2016-000155 Methods: To determine the clinical manifestations and ▸ Chronic pulmonary aspergillosis (CPA) is the outcome of pulmonary aspergillosis in a tertiary care commonest pulmonary manifestation as post-TB hospital a retrospective study was conducted from sequel. Received 10 August 2016 2004 to 2014 in patients admitted with pulmonary ▸ Overall patients had good outcome with CPA Revised 12 October 2016 aspergillosis at the Aga Khan University Hospital compared with subacute invasive pulmonary Accepted 10 November 2016 Karachi, Pakistan. aspergillosis (SAIA) and invasive pulmonary Results: Of the 280 cases with provisional diagnosis aspergillosis (IPA). of aspergillosis 69 met the inclusion criteria. The mean age was 45±15.7 years, 48 (69.6%) were men and 21 by copyright. (30.4%) had diabetes mellitus (DM). The average as allergic bronchopulmonary aspergillosis length of hospital stay (LOS) was 10.61±9.08 days. (ABPA) to subacute invasive aspergillosis Aspergillus fumigatus was the most common (42.0%), (SAIA) or as chronic necrotising pneumonia followed by Aspergillus flavus (28.9%). More than one- 1 third of patients previously had tuberculosis (TB) and invasive pulmonary aspergillosis (IPA). (39.13%). The commonest pulmonary manifestation Aspergillus fumigatus has been reported to be was chronic pulmonary aspergillosis (CPA) 47 (68.1%) responsible for more than 90% cases of inva- followed by invasive pulmonary aspergillosis (IPA) 12 sive aspergillosis.2 Aspergillus flavus, Aspergillus (17.4%) and subacute invasive aspergillosis (SAIA) 8 terreus, and Aspergillus niger are responsible for http://bmjopenrespres.bmj.com/ (11.6%). Surgical excision was performed in 28 the remaining invasive cases. The incidence patients (40.57%). Intensive care unit admission was of IPA globally is increasing due to increase required for 18 patients (26.08%). Case fatality rate in immunosuppressed patients but its was 14/69 (20.3%). DM, mean LOS and hypoxic true incidence is unclear in Pakistan. respiratory failure were identified as independent risk Aspergilloma is usually found in patients with factors of mortality on multivariate analysis. previously formed lung cavities, whereas Conclusion: A. fumigatus was the most frequent species found especially in patients with prior TB. CPA ABPA is a hypersensitivity reaction to was the commonest pulmonary manifestation seen as Aspergillus antigens, and is usually seen in fi 3 post TB sequel. Diabetes, hypoxic respiratory failure patients with atopy, asthma or cystic brosis. 1Department of Medicine, and increased LOS were independent predictors of Pulmonary aspergillosis has a variable course Section of Pulmonary and on September 29, 2021 by guest. Protected Critical Care, Aga Khan poor outcomes. Overall patients had good outcome of illness, severity and outcomes. University Hospital, Karachi, with CPA compared with SAIA and IPA. According to the WHO report in 2011, Pakistan around 1.2 million people in the world have 2Department of Pathology been estimated to have chronic pulmonary and Laboratory Medicine, aspergillosis (CPA) as a sequel to tuberculosis Aga Khan University, Karachi, Pakistan INTRODUCTION (TB) and most cases occur in South-East 3 fi 4 Department of Medicine, Aspergillosis is a spectrum of diseases cause Asia, Western Paci c and African regions. Aga Khan University, Karachi, by the Aspergillus spp. that are ubiquitous Scarce data is available on CPA as a post-TB Pakistan saprophytic fungi. The clinical spectrum of sequel and in structural lung diseases from developing countries. Correspondence to aspergillosis varies from the colonisation of Dr Nousheen Iqbal; the organism to the presence of fungus ball The aim of this study is to determine the [email protected] (aspergilloma) or an allergic response known clinical manifestations and outcomes of Iqbal N, Irfan M, Zubairi ABS, et al. BMJ Open Resp Res 2016;3:e000155. doi:10.1136/bmjresp-2016-000155 1 BMJ Open Resp Res: first published as 10.1136/bmjresp-2016-000155 on 16 December 2016. Downloaded from Open Access pulmonary aspergillosis in a tertiary care hospital in and/or culture of a specimen of tissue taken from a site Karachi, Pakistan to help understand the nature of of disease showed evidence of Aspergillus was labelled as disease and to improve the clinical outcome in this part proven IPA. While the probable and possible invasive of the world. infections were determined by a host factor, clinical signs and symptoms, and mycological evidence that encompassed culture and microscopic analysis.6 Patients METHODS were labelled ABPA depending on the criteria as This is a retrospective study in patients admitted with reported previously by Rosenberg et al.7 pulmonary aspergillosis at the Aga Khan University Hospital (AKUH), Karachi, Pakistan from January 2004 Laboratory methods to December 2014. The research protocol of this study Fungal cultures were performed at the Aga Khan was approved by the Ethical Review Committee of the University Clinical Laboratory, which is one of the Aga Khan University. All patients admitted with a diag- largest laboratories in Pakistan. This laboratory is a nosis of aspergillosis using International Classification of regional supranational laboratory for TB and regularly Disease, Ninth Revision codes (ICD-9 1173) were identi- participates in College of American Pathologists (CAP) fied. Information was collected from Health Information surveys for Mycology smear and culture. During the Management Services (HIMS), Department of AKUH. study period fungal smear was made using 10% potas- Data on demographics, comorbid, underlying lung con- sium hydroxide (KOH). Sputum and tracheal aspirates dition, radiographic and microbiological findings, mean for fungal culture were processed semiquantitatively by length of hospital stay (LOS), requirement of invasive picking up the most purulent portion and BAL were and non-invasive mechanical ventilation (NIMV), centrifuged at 1200×g for 10 min and the sediment was respiratory complications and in hospital mortality was used for microscopy and culture inoculation. The spe- collected on a predesigned form. cimen was inoculated on two plates of Sabouraud Inclusion criteria were (1) patient 18 years and above. Dextrose Agar (incubated at 28°C and 37°C), one (2) Positive sputum and/or positive bronchoalveolar plate of Sheep Blood Agar (incubated at 37°C), one lavage (BAL) (smear and/or culture) for Aspergillus plate of Potato Dextrose Agar (incubated at 28°C) and and/or positive lung histopathology suggestive of asper- one plate of Mycosel Agar containing cycloheximide by copyright. gillosis. (3) Chest X-ray/CT scan of the chest infiltrates (incubated at 28°C). All plates were reviewed by suggestive of aspergillosis. We excluded all patients with trained laboratory technologist and consultant micro- culture positive for Aspergillus other than respiratory spe- biologist daily for first week and then twice weekly for cimen, and whose medical records are with incomplete 3 weeks. information. Culture positive cases suggestive of colon- Culture plates were incubated and examined until isation only were also excluded. Outcomes were 4 weeks before reporting them as negative. Any fungal in-hospital mortality, mean LOS and respiratory growth was assessed by clinical microbiologist for clinical complications. significance and to rule out contamination and only sig- Patients were classified further into CPA, SAIA, IPA nificant isolates were further processed and identified. http://bmjopenrespres.bmj.com/ and ABPA. CPA was defined as one or more cavities with Identification of Aspergillus spp. was made on the basis or without a fungal ball or nodules on thoracic imaging, of gross appearance and microscopic morphology of the direct evidence of Aspergillus infection (microscopy or colonies.8 culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all Statistical analysis present for at least 3 months.5 CPA was further classified All analyses were conducted by using the SPSS (Release into two categories (1) single cavity with single fungal 19.0, standard version, copyright © SPSS; 1989–2002). A ball with no radiological progression over at least descriptive analysis was performed for demographic fea- 3 months of observation is labelled as single (simple) tures presented as mean±SD for quantitative variable pulmonary aspergilloma and (2) patients with one or that is, age and lengths of hospital stay. Number (per- on September 29, 2021 by guest. Protected more pulmonary cavities containing one or more asper- centage)