HRCT IN DETECTION OF NTM PULMONARY INFECTION IN IMMUNOCOMPETENT PATIENTS: OUR EXPERIENCE.

1. HRCT IN DETECTION OF NTM PULMONARY INFECTION IN IMMUNOCOMPETENT PATIENTS: OUR EXPERIENCE. T.Valente, M.Marino, G.Rea, A.Di Matteo, S. Urciuolo, R.Muto Department of Radiology, Monaldi Hospital, Naples, Italy

2. NTM Infection Group Name Characteristics I Photochromogens Colonies require 2–4 weeks to grow in culture and change from colorless to yellow on exposure to light; M kansasii is the most common pulmonary pathogen in this group II Scotochromogens Colonies require 2–4 weeks to grow in culture and change from yellow to orange on exposure to light; these organisms (M gordonae, M szulgai) are rare pulmonary pathogens III Nonphotochromogens Colonies require 2–4 weeks to grow in culture, are beige or white, and do not change color on exposure to light; this group includes M avium-intracellulare (the most common pulmonary pathogen) and M xenopi IV The rapid growers Colonies are visible after 3–5 days of culture and do not change color on exposure to light; these organisms (M fortuitum, M chelonae) are uncommon pulmonary pathogens • a group of low-grade pathogens omnipresent in the environment(water, soil, milk, fish, birds, animals) • mode of transmission : inhalation, ingestion, direct inoculation, human-to-human (rare); main source of pulmonary infection water vapour • In hospital setting infection may originate from biofilm sources (bronchoscopes) • Preexisting disease: smoking-related COPD, bronchiectasis, pneumoconiosis, diabetes mellitus, alcohol abuse, localized pulmonary fibrosis, INF-gamma deficit, cystic fibrosis • Clinical presentation is variable and non specific, the level of host immunity has a profound effect on the severity of infection CHEST 2004; 126:566-81 RADIOLOGY 2004; 231:880-86 RADIOLOGY 2005; 235:282-88 AM J RESP CRIT CARE MED 1997; 156:S21-25 RADIOGRAPHICS 1999; 19: 1487-503 Runyon Classification

3. Purposes of the Study • Estimate imaging (CXR, HRCT) at diagnosis • Understand diagnostic utility of conventional radiographic abnormalities • Characterize HRCT dominant patterns of infection • Imaging –pathologic correlation • Follow-up of the lesions encountered at radiological presentation

4. ATS/IDSA criteria 2007 for diagnosis of pulmonary NTM diseases Clinical and radiographic (both required): Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a HRCT scan AND Appropriate exclusion of other diagnoses, especially tuberculosis and mycosis Microbiological Positive culture results from at least two separately expectorated sputum samples. If results are non-diagnostic, consider repeat smears and cultures OR Positive culture results from at least one bronchial wash or lavage OR  Transbronchial or other lung biopsy with mycobacterial histopathological features (granulomatous inflammation or stainable acid-fast bacilli), positive culture for NTM or biopsy showing mycobacterial histological features, and ≥1 sputum or bronchial washings that are culture positive for NTM.  MATERIALS We retrospectively reviewed theCXR andHRCTexaminations (HRCT, slice thickness 1mm/interslice 10mm, bone filter) performed between Jan ’02- Dic ’08, on 56 immunocompetent patients (M/F-37/19; age range 41-83 ys) with diagnosis of NTM pulmonary infection confirmed by using American Thoracic Society criteria Am. J. Respir. Crit. Care Med. 2007

5. METHODS EVALUATED FINDINGS CXR Cavitations Foci of consolidations Small diffuse nodules Bronchiectasis Fibrosis with lobar volume loss Focal pleural thickening Mediastinal adenopathy Pleural effusion HRCT Small nodules (Ø ‹ 10mm) Nodules (Ø 10-30mm) Tree in bud Foci of consolidations Bronchiectasis Cavitary disease Pleural thickening Adenopathy 15/56follow up after therapy up to 20 months 4/15 correlation radiologic/pathologic on reseceted lobectomy gross specimens

6. RESULTS CT FINDINGS RUL ML RLL LUL LING LLL SMALL NODULES 14(26,5%) 11(20,1%) 5(9,5%) 9(17%) 9(17%) 5(9,5%) NODULES 8(31,6%) 4(15,8%) 4(15,8%) 5(21%) 3(10,5%) 2(5,3%) SEGM. CONSOL. 9(25%) 6(17,8%) 5(14,3%) 6(17,8%) 10(31,1%) 5(14,3%) LOBAR CONSOL. 3(30%) 3(30%) 0(0%) 2(20%) 0(0%) 2(20%) TREE-IN-BUD 8(41,2%) 6(29,4%) 4(23,5%) 6(29,4%) 4(23,5%) 3(11,8%) CAVITATION 16(46,6%) 6(16,7%) 5(16,7%) 4(13,3%) 2(6,7%) 3(10%) BRONCHIECTASIS 8(25%) 7(21,4%) 1(3,6%) 2(7,1%) 3(7,1%) 3(10,7%) 33/56 M. Kansasii (M/F-23/10; age 55-83ys) 23/56 MAC (M/F-9/14; age 41-72ys) CT characterized 2 lobar consolidations, 10segmental consolidations, 8 cavitated lesions,and 12 bronchiectasis areas not showed at CXR.

8. 2 patients: “hot tub lung” pattern • contaminated water in hot tub is aerosolized and inhaled causing hypersensitivity reaction (or a granulomatous response to infection? Maybe both processes) • occurs in previously healthy subjects • radiologic findings are typical of hypersensitivity pneumonitis • Primarily to aerosolized M. avium-intracellulare • radiographs show fine diffuse reticulonodular or miliary pattern • CT shows patchy areas of ground glass attenuation and/or poorly formed nodules of ground glass attenuation. Expiratory images may show airtrapping indicating an associated bronchiolitis

9. Hot tub lung 1: miliary form (small nodules 1-2 mm) with lamellar consolidations

10. Hot tub lung 2: poorly formed GGO micronodules Expiratory air trapping

11. CONSIDERATIONS NTM SMALL NODULES BRONCHIECTASIS CAVITATION M.Kansasii 30-39%upper lobe 30%right upper lobe 43%upper lobe MAC 50%middle lobe and lingula 30-50%middle lobe and lingula 33.3%middle lobe and lingula SMALL NODULES 78.6% CAVITATIONS 71.4% BRONCHIECTASIS 66.6% SEGMENT.CONSOLID. 66.6% SMALL NODULES 87% CAVITA’TIONS 13% BRONCHIECTASIS 81% SEGMENT. CONSOLID. 17% (Y.J.Jeong RADIOLOGY 2004) SMALL NODULES 70% CAVITATIONS 20% BRONCHIECTASIS 80% SEGMENT. CONSOLID. 75% (E.H.MooreRADIOLOGY1993)

12. small nodules consolidation cavitation bronchiectasis macronodules

13. RESULTS Follow up 15/56 8 MAC / 7 M. Kansasii 5/15 nodule cavitation (2 right upper lobe; 1 lingula; 1 middle lobe) 6/15 new bronchiectasis and increased number of preexisting 3/15 small nodules, consolidations and tree-in-bud reduction 2/15 unchanged pattern 4/15 disease progression – surgical treatment (lobectomy) Centrilobular nodules correspond to granulomas and caseous material at the level of the terminal and respiratory bronchioles; nodules > 10mm and lobar consolidation correspond to areas of central caseous granulomas, associated with nonspecific marginal inflammation and lymphocyte infiltration, which completely replaces the alveolar spaces. The wall of the cavitations consists of caseous material, epithelioid cells, multinucleated giant cells, granulomatous tissue and a fibrotic capsule.

14. day 0 18 months day 0 18 months

15. CONCLUSIONS (1/3) More frequent pattern in immunocompetent: • Diffuse small nodules • bronchiectasis • Segmental aonsolidation • cavitations “CLASSIC” fibrocavitary form * of upper lobes is more prevalent among older men with underlying chronic pulmonary disease, most cases are caused by M. Kansasii *J.J.Erasmus RADIOGRAPHICS 1999 *S.Field CHEST 2004 “Nodular -bronchiectatic (Nonclassic) Form* of middle lobe/lingula is more commonly seen among middle-aged /elderly women with no predisposing factors, most cases are caused by MAC *J.J.Erasmus RADIOGRAPHICS 1999 *S.Field CHEST 2004 Some of these patients may voluntarily suppress their cough,leading to poor drainage of secretions and engraftment of NTM, the so-called Lady Windermere syndrome* *Reich JM CHEST 1992

16. CONCLUSIONS (2/3) Less frequent pattern in immunocompetent: • Hypersensitivity pneumonitis –like (hot tube) • Solitary pulmonary nodule presents very much like a tuberculoma, and has to be differentiated from a carcinoma Solitary pulmonary nodule

17. CONCLUSIONS (3/3) • New nodules occur over time • Some macronodules can undergo cavitation • Some small nodules may disappear • Preexisting bronchiectasis tend to increase in size • New areas of dilatation can form over time BRONCHIECTASIS: CAUSE AND/OR EFFECT!!!!!!

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