Bronchiectasis, Cystic Fibrosis, Asthma Risk Factors for Aspergillosis

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However, Dr. cautioned that azoles interfere with the metabolism of

steroids. He advised clinicians to be aware that combined use may cause

adrenocortical suppression.

Dr. said he treats ABPA with combination therapy consisting of

high-dose inhaled steroids and usually a trial of itraconazole for 3 months, and

then monitoring clinical response carefully and doing liver function

tests. " If there's an improvement in symptoms and frequency of exacerbations

and

no evidence of liver toxicity, then we would continue. "

Bronchiectasis, Cystic Fibrosis, Asthma Risk Factors for Aspergillosis

Becky McCall

December 17, 2010 (Dubai, United Arab Emirates) — Aspergillus infects as

many as 10% of patients with bronchiectasis. The fungus has a unique

self-defense mechanism against phagocytes, allowing it to survive in the lung,

according to a presentation here at the World Allergy Organization 2010

International Scientific Conference.

Neil , MD, consultant in respiratory and general medicine at the

London Chest Hospital and the Royal London Hospital in the United Kingdom, gave

a presentation addressing diagnosis and treatment related to aspergillus

in lung diseases.

" We need to be aware that many patients with asthma, bronchiectasis, or

cystic fibrosis have another pathology as well their primary problem.

Identifying these complications has important clinical implications, " he said.

The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in

patients with bronchiectasis is variable but is usually between 1% and 10%, Dr.

said.

He described his experience with aspergillus-related diseases. " [Computed

tomography] scans of ABPA show central bronchiectasis with infiltrates

around the bronchi...where infection has taken hold. We know aspergillus causes

other lung diseases as well. Some patients get aspergillomas, or invasive

aspergillosis which develop into aspergilloma, " commented Dr. .

He explained why aspergillus causes so many lung problems. " There are other

fungi, for example, candida, which is far more common, yet we don't see

candida entering cavities, " he commented.

" Aspergillus is a soil saprophyte which lives in rotting vegetation

particularly, where it is phagocytosed by protozoa. Due to this, aspergillus has

developed defense mechanisms against protozoa, which incidentally also act

against lung phagocytes.

" The killing of aspergillus in the lung is prevented by complement, which

is present in high amounts in the airways of people with asthma and

bronchiectasis. These high levels of complement prevent the lung dealing with

aspergillus, " Dr. explained.

He emphasized that clinicians need to be aware that patients with

bronchiectasis, asthma, or cystic fibrosis may have another pathology present.

" In

the UK, the bronchiectasis guidelines recommend that patients with

bronchiectasis are screened for ABPA, but this only has a level D of evidence. "

He

suggested having a high level of suspicion for aspergillosis.

According to Dr. , ABPA can be identified by the presence of central

bronchiectasis, positive skin-prick tests to aspergillus, raised total

immunoglobulin E (IgE), and raised specific IgE against aspergillus.

Reviews often suggest treating ABPA with regular oral corticosteroids, but

Dr. questioned this approach, as the recommendation was really based

on case series of patients with ABPA that were weighted toward patients

with severe ABPA. " I question whether this is of relevance to patients with

milder forms of the disease. Also, in these case series...inhaled steroids

or antifungals [often] were not used. "

He said that the best-controlled evidence was with azoles, and in

particular, itraconazole (Sporanox; Janssen Pharmaceutica). He referred to a

Cochrane review on the use of azoles in ABPA, which " showed that exacerbations

of

ABPA requiring steroids were markedly reduced from 1.3 to 0.4 per patient.

They were more likely to have a decrease in IgE levels. "

However, Dr. cautioned that azoles interfere with the metabolism of

steroids. He advised clinicians to be aware that combined use may cause

adrenocortical suppression.

Dr. said he treats ABPA with combination therapy consisting of

high-dose inhaled steroids and usually a trial of itraconazole for 3 months, and

then monitoring clinical response carefully and doing liver function

tests. " If there's an improvement in symptoms and frequency of exacerbations

and

no evidence of liver toxicity, then we would continue. "

He mentioned that newer antifungals are available; notably, voriconazole

(Vfend; Pfizer) and posaconazole (Noxafil; Schering-Plough). " However, these

are expensive, and it is still unclear whether these are very effective

for ABPA. "

Treating the bronchiectasis as well as the aspergillus was also important,

Dr. added. " Apart from flare-ups due to aspergillus, [the patients]

get flare-ups due to bacterial-induced exacerbations, so they may require

nebulized antibiotics and azithromycin (Zithromax; Pfizer). "

Dr. said that in contrast to some of the recommendations about use

of regular oral steroids, he tries to restrict their use to exacerbations in

patients with less severe infections. " [These patients] actually do very

well on inhaled steroids and antifungals. However, we do have some patients

whom we cannot take off oral steroids. "

ABPA is also found in cystic fibrosis (CF), although incidence figures

depend on the diagnostic criteria. " There's evidence that colonization by

aspergillus does worsen prognosis. "

Dr. cited 2 large studies looking at incidence of ABPA in CF. A US

study found a 2% incidence, whereas a European database found an incidence

of 7.8%.

With reference to a Cystic Fibrosis Foundation consensus conference on ABPA

in CF held in 2001, Dr. said that clinicians should be suspicious

of ABPA in CF in patients older than 6 years. " [The recommendation was to

measuring] total IgE annually, and if this was more than 500 U/mL, then to

conduct skin tests. "

According to the consensus reached at the conference, diagnosing ABPA

includes noting a change in symptoms not attributable to another cause, an

increase in total IgE, a positive skin test to aspergillus, and either IgE

antibody to aspergillus or a new infiltrate on chest x-ray or computed

tomography scan. " This isn't easy in CF because these patients suffer from

repeated

infections and new infiltrates, and deciding whether this is bacterial or

due to ABPA is quite a challenge, " Dr. said.

He also commented that much of the evidence that clinicians base their

practice on is of low quality. " I think we need research on the use of azoles

in bronchiectasis and cystic fibrosis. "

Glenis Scadding, MD, consultant physician in allergy and rhinology, Royal

National Throat, Nose, and Ear Hospital in London, United Kingdom, noted

that aspergillus needs to be considered a possibility when dealing with

difficult asthma and difficult rhinosinusitis — usually polypoid

rhinosinusitis.

" In a patient with both of these together, it's one of what I call the 3

'A's: aspergillus, aspirin (aspirin-exacerbated respiratory disease), and the

third 'A' is ANCA (anti-neutrophil cytoplasmic antibodies) — thinking

about Churg-Strauss syndrome.

" I occasionally come across ABPA, but usually as an addition to allergic

fungal sinusitis, it's probably the same pathology, but in the upper airway.

The fact that the sinus disease and the aspergillus infection can occur

together is not always recognized, " Dr. Scadding commented.

" The association with activity of aspergillus in the soil is a fascinating

mechanism [for infection], " he added.

" It's also worth noting that deaths in asthma tend to be seasonal, with a

peak at the end of the summer. The idea that these are fungally sensitized

patients is gaining currency. There's a flurry of asthma deaths at this time

of year, " Dr. Scadding noted.

Dr. and Dr. Scadding have disclosed no relevant financial

relationships.

World Allergy Organization 2010 International Scientific Conference.

Presented December 7, 2010.

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Authors and Disclosures

Journalist

Becky McCall, MSc

Becky McCall, MSc, is a freelance writer for Medscape.