CHAPTER Fungal Infection in the Lung 52 Udas Chandra Ghosh, Kaushik Hazra INTRODUCTION The following risk factors may predispose to develop Pneumonia is the leading infectious cause of death in fungal infections in the lungs 6 1, 2 developed countries . Though the fungal cause of 1. Acute leukemia or lymphoma during myeloablative pneumonia occupies a minor portion in the immune- chemotherapy competent patients, but it causes a major role in immune- deficient populations. 2. Bone marrow or peripheral blood stem cell transplantation Fungi may colonize body sites without producing disease or they may be a true pathogen, generating a broad variety 3. Solid organ transplantation on immunosuppressive of clinical syndromes. treatment Fungal infections of the lung are less common than 4. Prolonged corticosteroid therapy bacterial and viral infections and very difficult for 5. Acquired immunodeficiency syndrome diagnosis and treatment purposes. Their virulence varies from causing no symptoms to death. Out of more than 1 6. Prolonged neutropenia from various causes lakh species only few fungi cause human infection and 7. Congenital immune deficiency syndromes the most vulnerable organs are skin and lungs3, 4. 8. Postsplenectomy state RISK FACTORS 9. Genetic predisposition Workers or farmers with heavy exposure to bird, bat, or rodent droppings or other animal excreta in endemic EPIDEMIOLOGY OF FUNGAL PNEUMONIA areas are predisposed to any of the endemic fungal The incidences of invasive fungal infections have pneumonias, such as histoplasmosis, in which the increased during recent decades, largely because of the environmental exposure to avian or bat feces encourages increasing size of the population at risk. This population the growth of the organism. In addition, farmers and includes the patients of cancers of immune cells of the gardeners are at higher risk of acquiring sporotrichosis blood, bone marrow, and lymph nodes, and those with because of their chance of cuts or puncture wounds while human immunodeficiency virus (HIV) infection, as they working with soil. are immunosupressed. With advances in critical care medicine and introduction The basic pulmonary pathologic process again can be of broad-spectrum antibiotics, the incidence of invasive broadly classified as (a) allergic manifestation or (b) actual fungal infections in intensive care is on the rise, especially infection 5, 7 in patients with immunosuppression 5. TLR1 (Toll like receptors) and TLR6 polymorphisms in the recipient have been associated with susceptibility Table 1: Fungi causing Pneumonia to invasive aspergillosis after allogeneic stem cell transplantation.5 Endemic fungal pneumonia pathogen The invasive fungal infections (termed mycoses) can be Histoplasma capsulatum causing histoplamosis. divided into two broad categories: endemic mycoses and Coccidioides immitis causing coccidioidomycosis. opportunistic mycoses (Table 1). Blastomyces dermatitidis causing blastomycosis. True pathogenic or endemic fungi Paracoccidioides brasiliensis causing The endemic pathogens that most frequently infect healthy paracoccidioidomycosis individuals. True pathogenic fungi produce a different Opportunistic fungal pneumonia pathogen form in tissue or at 37°C in contrast to mycelial form in Candida spp. causing candidiasis culture at 25-30°C. These fungi are referred to as dimorphic fungi and include Histoplasma capsulatum, Blastomyces Aspergillus spp. causing aspergillosis dermatitidis, Coccidioides immitis, Paracoccidioides Mucor spp. causing mucormycosis brasiliensis, Penicillium marneffei and Sporothrix Cryptococcus neoformans causing cryptococcosis schenckii. Fortunately, they are not commonly found in the Indian subcontinent and are natural inhabitants Zygomycetes Table 2: ISHAM Diagnostic Criteria for ABPA These are the most common fungal infections in lung in 233 our country- Predisposing conditions (one must be present): Asthma PULMONARY ASPERGILLOSIS According to the lung invasion or allergic response of Cystic fibrosis (CF) lung to aspergillus species, the pathogenic reactions in Obligatory criteria (both must be present): human beings can be varied like 4 Aspergillus skin test positivity or detectable IgE levels 1. Allergic alveolitis - by inhalation of high density of against Aspergillus fumigatus spores Elevated total serum IgE concentration (typically >1000 IU/mL, but if the patient meets all other criteria, 2. Allergic broncho pulmonary aspergillosis (ABPA). an IgE value <1000 IU/mL may be acceptable) 3. Aspergilloma - Colonisation in damaged lung CHAPTER 52 Other criteria (at least two must be present): parenchyma. Precipitating serum antibodies to A. fumigatus 4. Invasive Aspergillosis - in immunodeficient Radiographic pulmonary opacities consistent with individuals. ABPA 5. Mixed syndromes Total eosinophil count >500 cells/microL in glucocorticoid-naïve patients (may be historical) ABPA This is an immune mediated bronchial pathology, of North and South America. H. capsulatum and B. manifested in susceptible individual. dermatitidis have a worldwide distribution. Manifestations are haemoptysis and episodic wheezing, In India, histoplasmosis and blastomycosis are reported mimicking acute asthmatic episode. from different states, but Penicilliosis marneffei is Diagnostic criteria of ABPA11 restricted to Manipur state. There is only one report of Although not prospectively validated, we favor the systemic sporotrichosis due to S. schenckii var. luriei and following diagnostic criteria proposed by the International 7,8 represents the only report from an Asian country . Society for Human and Animal Mycology (ISHAM) P. marneffei is restricted to south-east Asia possibly working group for ABPA that simplify prior diagnostic 9,10 remaining with its habitat bamboo rats . Along with schema (Table 2): emergence of AIDS in India, histoplasmosis is increasingly reported. Stages of ABPA4,13-15 1. acute stage Opportunistic fungal infections involve ubiquitous fungi and occur predominantly in individuals whose immune 2. stage of remission systems are compromised. These include species like 3. stage of exacerbation Aspergillus, Candida, Cryptococcus and Zygomycetes (big four).6,11 Invasive pulmonary aspergillosis and 4. stage of steroid dependent asthma systemic candidiasis are the most prevalent opportunistic 5. stage of fibrosis fungal infections. These infections do not follow any particular geographic distribution and are seen with RADIOLOGICAL PICTURE4,16-18 increasing frequency worldwide. Chest Xray However, recently changes have occurred, and newer Massive areas of consolidation pathogens are being recognized especially with Inflamed vascular and bronchial walls (Tram line the emergence of AIDS. Sometimes, it is not just a shadows) single fungus, but rather a combination of fungi i.e. species under Candida, Cryptococcus, Pneumocystis, Blocked bronchi with fungal debris (Tooth paste shadows) Histoplasma, Coccidioides, Aspergillus and zygomycetes, & gloved finger appearance) which may produce concomitant and/or successive Ring shadows (Bronchiectasis) opportunistic systemic fungal infections. Parenchymal appearance (Nodular shadows) Diagnosis of fungal infections Local areas of atelectesis & emphysema The diagnosis of this disease entity is based on indirect evidences like CT scan bronchogram: a. Skin hypersensitivity test Hallmark is proximal bronchiectasis with distal sparing. 16,19,20 b. Serological evidence of raised antibody titre Management of ABPA Steroid and Antifungal (Itraconazole or Amphotericin B). c. Convincing demonstration of fungi from body fluids or tissue specimens. Steroid is used in acute phase with tapering dose till the resolution. 234 Resolution Pneumocystis jiroveci Pneumonia23,24 Typically resolution has been defined as- Pneumocystis is a unicellular fungus. 1. Control of asthmatic attacks Pneumocystis jiroveci pneumonia (PJP), previously known as Pneumocystis carinii pneumonia (PCP), is still 2. Reduction of IGE level more than 35% with the most common opportunistic infection in HIV positive reduction of peripheral eosinophilia patients, though the incidence is decreasing. 3. Disappearance of pulmonary opacities Before the widespread use of prophylaxis for P Aspergilloma4 jiroveci pneumonia (PJP), the frequency of Pneumocystis Growth of aspergillus fungal ball inside pre existing infection in lung transplant patients and HIV patients pulmonary cavities (e.g. TB, sarcoid, cavities in RA). before starting HAART was very high. Clinical features are characterised by- The taxonomic classification of the Pneumocystis genus Recurrent Hemoptysis with recurrent respiratory tract was debated and previously thought to be a protozoan infection. but biochemical analysis of the nucleic acid composition of Pneumocystis rRNA and mitochondrial DNA identified Diagnosis: confirmed by PULMONOLOGY it as a unicellular fungus rather than a protozoan. Chest X ray-mass within cavity with air cresent level on the top, especially in upper lobe (Monods sign) Symptoms of PJP includes progressive exertional dyspnea, fever, nonproductive cough, chest discomfort Positive precipitin test to Aspergillus antigen The physical examination findings of PJP are nonspecific Demonstration of fungal hyphae in respiratory secretions and includes tachypnea, tachycardia, and pulmonary or from tissue specimen. symptoms are few mild crackles and rhonchi but Raised IgE levels. otherwise normal findings Treatment Diagnosis is done from chest x-ray CT scan thorax, Only observations for asymptomatic