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PLoS One ; 17(8): e0272034, 2022.
Article in English | MEDLINE | ID: covidwho-2079709


RATIONALE: Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects. OBJECTIVES: To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler. METHODS: Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation. RESULTS AND DISCUSSION: Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV1 post inhalation. The serum HCQ concentration remained below 10 µg/L in all samples. CONCLUSION: Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.

COVID-19 , Hydroxychloroquine , Administration, Inhalation , COVID-19/drug therapy , Dry Powder Inhalers , Healthy Volunteers , Humans , Hydroxychloroquine/adverse effects , Powders , SARS-CoV-2
Journal of Heart & Lung Transplantation ; 41(4):S54-S54, 2022.
Article in English | Academic Search Complete | ID: covidwho-1783340


In April 2020 COVID-19 lockdown measures were instigated leading to a dramatic drop in non-COVID respiratory virus infections (RVI). This provided a unique situation to assess the impact of RVI on annual FEV1 decline, episodes of temporary drop in lung function suggestive of infection (TDLF) and CLAD in lung transplant recipients (LTR). All lung function tests (LFT) of LTR transplanted between 2009-April 2020 were used from post-transplant baseline onward. LFT were censored after COVID-19 infection. Weekly RVI counts from the virology department defined RVI pressure over time. TDLF was defined as sudden, reversible FEV1 drop compared to previous 4 values (any TDLF ≥10% and ≥200ml, severe TDLF ≥20% and ≥500ml). Annual FEV1 decline was estimated using linear mixed effects models with separate estimates for 2009/20 and 2020/21. Effect modification by TDLF frequency of individual LTR (two subgroups, split at median) and RVI pressure was tested. Rates of CLAD and TDLF were analyzed over time. 479 LTR (12,775 LFT) were included. Annual FEV1 change in 2009/20 was -114ml [95%CI -133;-94], while in 2020/21 this was significantly less: 5ml [-38;48] (p<0.001). RVI pressure significantly affected FEV1 level (an increase in weekly RVI-count of 10 leading to a 7ml [-10;-5] lower FEV1 (p<0.001). FEV1 decline in 2009/20 was faster in frequent TDLF LTR vs. infrequent (-150ml [-181;-120] vs. -90ml [-115;-65] p=0.003 Fig A). 2020/21 showed significant decreases in number of any TDLF (OR 0.53 [0.33;0.85], p=0.008) and severe TDLF (OR 0.34 [0.16;0.71] p=0.005) and numerically lower CLAD (OR 0.53 [0.27;1.02] p=0.060). Effect modification by RVI pressure (Figures B-D) indicated an association between the events and RVI. During the lockdown year 2020/21 the broad decline in RVI coincided with substantially less FEV1 decline, TDLFs and possibly CLAD. All these outcomes were moderated by RVI pressure suggesting an important role for RVI in lung function decline in LTR. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)