Respiratory Muscle Overloading and Dyspnoea During Bronchoconstriction in Asthma: Protective Effects of Fenoterol

Whether, and to what extent, β₂-agonists protect against respiratory muscle overloading and breathlessness during bronchoconstriction remains to be defined in patients with asthma. In a double blind placebo-controlled study, 100 μg of fenoterol were administered to six stable asthmatics before a bronchial provocation test, performed by inhaling doubling concentrations of histamine from a Devilbiss 646 nebulizer. We recorded breathing pattern (tidal volume V_T, inspiratory time T_I, total time of the respiratory cycle T_TOT), inspiratory capacity (IC), dynamic pleural pressure swing (P_plsw), total lung resistance (R_L) and FEV₁. V_Twas expressed both in actual values and as % of IC. Changes in V_T(%IC) during histamine inhalation reflected changes in dynamic end-inspiratory lung volume (EILV). P_plswwas expressed as % of maximal (the most negative in sign) pleural pressure, obtained under control conditions during a sniff manoeuvre (P_plsn). P_plsw(%P_plsn) is an index of inspiratory muscle effort. The test ended when the concentration of histamine which caused a decrease in FEV₁of ≥40% post-saline was reached. Dyspnoea rating was scored by a modified Borg scale. At the ultimate degree of bronchoconstriction (UDB) with histamine: (i) decrease in FEV₁was similar after placebo and fenoterol, while increase in R_Lwas lower after fenoterol (P<0.005); (ii) V_T(%IC) increased less after fenoterol (P<0.027); (iii) increases in P_plsw(%P_plsn) was lower after fenoterol (P<0.001); (iv) ΔBorg (from saline) was lower (P<0.01) after fenoterol; (v) differences in ΔBorg, from placebo to fenoterol, related to concurrent changes in V_T(%IC) (r²=0.67). In conclusion, at UDB 100 μg of fenoterol produced a beneficial effect on the degree of inspiratory muscle loading and breathlessness, an effect greater than it would be expected from measuring FEV₁alone.