1 Approach to Pulmonary Problems of Immunosuppressed Patients Dr.Özlem Özdemir Kumbasar

2 Pulmonary complications are frequent and life-threatining problems in immunocompromised patients. Early diagnosis for optimal treatment is very important. Empirical therapy should be started as soon as possible for most of the patients.

3 The number of immunosuppressed patients has increased recently: Neutropenia following cancer chemotherapy Hematological malignancy Solid organ transplantation Hematopoietic stem cell transplantation Immunosuppressive treatments for auto-immune diseases HIV infection …………

4 Rapid diagnosis is necessary because of high mortality. To obtain an etiological diagnosis is usually difficult and sometimes requires invasive diagnostic methods.

5 To obtain an etiological diagnosis is difficult. Because: Clinical findings may be silent Clinical picture is nonspecific Infectious and non-infectious diseases can be seen together More than one infectious agent may be responsible for the pulmonary problem

6 Sometimes invasive diagnostic methods are necessary. But, usually these procedures are difficult for these patients: General condition of the patient? Respiratory failure? Thrombocytopenia?

7 Approach to Pulmonary Complications in an Immunosupressed Patient Clinical evaluation Radiologial findings Empirical treatment Diagnostic tests

8 Clinical Evaluation Type of imunosuppression Neutropenia Humoral immunodeficiency Cellular immunodeficiency

9 Neutropenia Gram-negative rods S.aureus Coagulase-negative staphylococci Viridans streptococci Aspergillus

10 Neutropenia Long lasting profound neutropenia: Fungi Multiresistent gram negative rods (P.aeruginosa, S.maltophilia) and other bacteria P.jiroveci Viruses …………… Noninfectious diseases Alveolar bleeding COP Lesions due to chemo- or radiotherapy Malign infiltration ……………

11 Humoral immunosuppresion Pneumococcus H.influenzae

12 Cellular immunosuppression M.tuberculosis P.jiroveci Legionella Nocardia Nontuberculous mycobacteria Fungi Viruses

13 Clinical evaluation Medical history Type, intensity and duration of immunosuppression Previous treatments Prophylaxis CAP? HAP? Condition of the hospital

14 Clinical evaluation Timing of the complication HSCT SOT

15 Timing HSCT Preengraftment phase (0-30days) Bacteria, Candida, Aspergillus DAH, IPS, engraftment syndrome Early postengraftment phase (30-100days) CMV, PCP, Aspergillus IPS Late posttransplant phase (>100days) CMV, VZV, community acquired viruses, pneumococcus, H.influenzae, tuberculosis BOOP PTLD BO

16 Timing SOT 0-1 month: HAP Fungi 1-6 months: Aspergillus PCP CMV, other viruses Nocardia >6 months: CAP Tuberculosis

17 Clinical evaluation Clinical behavior of the complication Acute Bacteria Viruses PCP (nonHIV patients) Pulmonary edema, DAH, PTE…. Subacute/chronic Aspergillus CMV Nocardia Tuberculosis

18 Symptoms Symptoms are usually nonspecific Cough Fever Dyspnea Skin lesions-bacteria, fungi Nodules-Aspergillus, Nocardia Invasive sinusitis-mucor, Aspergillus, Fusarium Corioretinitis-CMV Brain abscess-Nocardia, Aspergillus, Pseudomonas, Toxoplasma

19 Radiological findings To evaluate radiological clues is vey important for planning rapid and optimal empirical therapy The main radiological patterns: Focal infiltrate-consolidation Nodular infiltrates Diffuse interstitial infiltrates

20 Additional radiological findings Cavitation Pleural effusion Atelectasis Lymphadenopathy Pneumothorax

21 Acute/focal infiltrates Bacteria Aspergillus Legionella Subacute-chronic/focal infiltrates Aspergillus Nocardia M.tuberculosis, MAI

22 Acute/nodular(+cavity) infiltrates Bacterial lung abscess Legionella Subacute-chronic/nodular (+cavity) Tuberculosis Nocardia Aspergillus Cryptococcus

23 Acute/diffuse interstitial infiltrates CMV P.jiroveci Subacute-chronic/diffuse intertitial CMV P.jiroveci RSV Miliary tuberculosis

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29 Noninfectious disorders Diffuse Pulmonary edema BOOP-COP NSIP LIP Drug induced pneumonitis Lymphangitic metastasis DAH IPS Radiation toxicity PAP

30 Noninfectious disorders Nodular + cavity Malignancy Septic embolism Kaposi sarcoma Posttransplant lymphoprolipherative disorder

31 Noninfectious disorders Focal BOOP-COP Radiation toxicity Pulmonary embolism and infarctus Phantom tumor Primary/metastatic tumor Atelectasis Kaposi

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33 Computed tomography detects pulmonary iniltrates earlier than chest x-ray. CT gives valuable information about characteristics of the pulmonary infiltrate. The diagnosis of pulmonary aspergillosis, PCP, CMV pneumonia could be suspected from the typical CT findings.

34 CT findings of invasive pulmonary aspergillosis Single or multiple nodules Mass like appearence Consolidation-especially pleural based, wedge shaped Halo sign Cavitation Air-crescent sign

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39 Similar BT findings may be seen in other invasive fungal infections, nocardiosis.

40 Halo sign- IPA->%60 (early finding) Pulmonary zygomycosis-%25

41 Reverse halo sign Central ground-glass opacity, surrounding consolidation Reverse halo sign may be seen in COP

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patients with fungal pneumonia Reverse halo sign in 8 patients (7- zygomycosis; 1 aspergillosis) Reverse halo sign was detected in 19% of patients with zygomycosis and <1% of aspergillosis.

44 PCP-CT findings: Ground glass opacities Interlobular septal thickening Cystic lesions

45 PCP

46 OP

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