Regional deposition of aerosolized interferon-gamma in pulmonary tuberculosis.
OBJECTIVE
Aerosol interferon-gamma (IFN-gamma) is a potential immunomodulator in the treatment of pulmonary tuberculosis (TB). Previous investigations demonstrated conversion of sputum smears in five patients with multidrug-resistant TB after 12 treatments over 1 month, and induction of signaling molecules in 10 of 11 drug-sensitive TB patients using BAL. The objective of the current study was to evaluate particle size and deposition pattern in patients with TB receiving aerosol IFN-gamma treatment.


METHODS
Particle size was determined with a cascade impactor, and deposition of IFN-gamma mixed with (99m)Tc-labeled human serum albumin was assessed using a gamma camera. Local levels of IFN-gamma were measured in BAL using enzyme-linked immunosorbent assays. Study patients/intervention: Fourteen patients with pulmonary TB received IFN-gamma aerosol (500 micro g) for 12 treatments in addition to antimycobacterial therapy with BAL before and after IFN-gamma aerosol treatment. Eight patients with minimal-to-moderate parenchymal involvement underwent deposition studies. Deposited (99m)Tc-labeled IFN-gamma aerosol was partitioned between upper airways and lungs using attenuation correction measurements. (133)Xe equilibrium scanning, (133)Xe washout, and (99m)Tc- macroaggregate injection defined regional lung volume, ventilation, and perfusion.


RESULTS
Upper airway deposition was significant often exceeding lung deposition (53.9 +/- 7.09 micro g vs 35.8 +/- 2.73 micro g, respectively [mean +/- SE]). IFN-gamma levels measured in BAL fluid were significantly increased with aerosol treatment (0.83 +/- 0.43 micro g before vs 24.76 +/- 8.71 micro g after, p </= 0.017), and IFN-gamma levels correlated with regional deposition of IFN-gamma aerosol (r = 0.823). Four-quadrant analysis of regional lung deposition best correlated with regional perfusion (r = 0.422, p = 0.013) with penetration of aerosol into areas of obvious radiographic infiltration on chest radiograph.


CONCLUSIONS
Aerosol therapy with IFN-gamma in patients with pulmonary TB is widely distributed and results in significant enhancement of IFN-gamma levels in the lower respiratory tract. In patients without lung destruction, IFN-gamma aerosol may be an adjuvant to enhance the local immune response.
Condos
Rany
R
Bellevue Chest Service, Division of Pulmonary and Critical Care Medicine, NYU School of Medicine, New York, USA. rany.condos@med.nyu.edu
Hull
Frank P
FP
Schluger
Neil W
NW
Rom
William N
WN
Smaldone
Gerald C
GC
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000493:pharmacokinetics / Q000627:therapeutic use; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011336:Probability; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging* / Q000188:drug therapy*
D000336:Aerosols; D007371:Interferon-gamma