Although patients receiving systemic corticosteroid therapy are more susceptible to secondary infection than patients not receiving corticosteroids, administration via the inhaled route minimizes this risk. Corticosteroid therapy can mask the symptoms of infection and should not be used in cases of bacterial, fungal, or viral infections that are not adequately controlled by anti-infective agents, except in life-threatening circumstances. Fluticasone; salmeterol should be avoided in patients with tuberculosis infections of the respiratory tract if possible. The incidence or course of acute bacterial or viral infection is probably minimally affected by inhaled corticosteroids in immunocompetent individuals; however, close monitoring of patients with immunosuppression is recommended if treatment with an inhaled corticosteroid is necessary.
Studies reporting exacerbations requiring OCS showed no difference between the two add-ons, but our confidence in the effect was low due to inconsistency between studies and because the confidence intervals ( CI ) included significant benefit of either treatment ( odds ratio ( OR ) , 95% CI to ; 1753 participants; 3 studies); three more people per 1000 might have an exacerbation on LAMA, but the CIs ranged from 29 fewer to 61 more. Imprecision was also an issue for serious adverse events and exacerbations requiring hospital admission, rated low (serious adverse events) and very low quality (exacerbations requiring hospital admission), because there were so few events in the analyses.
The delivery device should be carried between use and actuated at the frequency indicated in the instructions for use. Simulation of dropping the delivery device and the robustness of any lockout mechanism should be investigated. The dropping simulation should be performed towards the end of the life of the product (. at dose 180 for a 200-dose product) in order to assess the effect of drug accumulated on the mouthpiece, or any other part of the device, during the lifetime of the device being dislodged. If the device is designed to have the mouthpiece removed for periodical cleaning, testing should be performed both with the mouthpiece removed and cleaned in accordance with instructions for use during the test, and, as a worst case, without removal and cleaning. Significant variations in the delivered dose and/or fine particle mass should be fully discussed in terms of the safety and efficacy of the product. Appropriate handling instructions to the patients should be established, based on the results obtained.