TY - JOUR
T1 - Allergen challenge and deposition of nedocromil sodium in asthma
AU - Laube, Beth L.
AU - Lin, Ta Chun
AU - Valleteau, Anne
AU - Dalby, Richard N.
AU - Diemer, Fiona B.
AU - Togias, Alkis G.
PY - 2002
Y1 - 2002
N2 - We examined whether the acute protective effect of nedocromil sodium aerosol could be enhanced by increasing the deposition uniformity of the drug in the lungs of adult patients with allergic asthma. Ten patients with mild-to-moderate asthma were challenged with the same doses of allergen on two occasions in a randomized manner. Thirty minutes before these challenges, patients inhaled 4 mg nedocromil sodium, admixed with the radioisotope 99mtechnetium. Radiolabeled drug was inhaled during slow (25.4 ± 4.6 L/min) and faster (58.0 ± 7.3 L/min) inhalations from a 700 ml holding chamber. Percent changes in FEV1 at the same top dose of allergen on the two treatment visits were compared. Lung deposition fraction (LDF) and indices of distribution uniformity, quantified from gamma camera images, were also compared. Acute protection against allergen challenge was similar and complete after slow or faster inspiration of nedocromil sodium. Mean (±SD) allergen-induced changes in FEV1 were -1.05 ± 2.78% and -0.39 ± 2.80%, respectively, compared to -26.30 ± 8.49% on a screening challenge (no drug). Mean LDF was also similar on the two visits, averaging 16.4 ± 4.6% and 16.1 ± 7.2% of administered drug, respectively. Distribution of nedocromil sodium was most uniform after slow inspiration, but increased uniformity was not related to enhanced protection. Complete protection against acute bronchoconstriction induced by inhaled allergen can be obtained with 4 mg of nedocromil sodium aerosol, inhaled from a large volume holding chamber, 30 min before the exposure, and at inspiratory flow rates between ∼20-60 L/min. Protection does not appear to be enhanced by increased uniformity of drug distribution within the lungs.
AB - We examined whether the acute protective effect of nedocromil sodium aerosol could be enhanced by increasing the deposition uniformity of the drug in the lungs of adult patients with allergic asthma. Ten patients with mild-to-moderate asthma were challenged with the same doses of allergen on two occasions in a randomized manner. Thirty minutes before these challenges, patients inhaled 4 mg nedocromil sodium, admixed with the radioisotope 99mtechnetium. Radiolabeled drug was inhaled during slow (25.4 ± 4.6 L/min) and faster (58.0 ± 7.3 L/min) inhalations from a 700 ml holding chamber. Percent changes in FEV1 at the same top dose of allergen on the two treatment visits were compared. Lung deposition fraction (LDF) and indices of distribution uniformity, quantified from gamma camera images, were also compared. Acute protection against allergen challenge was similar and complete after slow or faster inspiration of nedocromil sodium. Mean (±SD) allergen-induced changes in FEV1 were -1.05 ± 2.78% and -0.39 ± 2.80%, respectively, compared to -26.30 ± 8.49% on a screening challenge (no drug). Mean LDF was also similar on the two visits, averaging 16.4 ± 4.6% and 16.1 ± 7.2% of administered drug, respectively. Distribution of nedocromil sodium was most uniform after slow inspiration, but increased uniformity was not related to enhanced protection. Complete protection against acute bronchoconstriction induced by inhaled allergen can be obtained with 4 mg of nedocromil sodium aerosol, inhaled from a large volume holding chamber, 30 min before the exposure, and at inspiratory flow rates between ∼20-60 L/min. Protection does not appear to be enhanced by increased uniformity of drug distribution within the lungs.
KW - Acute antigen response
KW - Aerosol deposition
KW - Asthma
KW - Nedocromil sodium
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U2 - 10.1089/08942680260473498
DO - 10.1089/08942680260473498
M3 - Article
C2 - 12581508
AN - SCOPUS:0036964520
SN - 0894-2684
VL - 15
SP - 415
EP - 425
JO - Journal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung
JF - Journal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung
IS - 4
ER -