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Standard care in severe SARS-CoV-2 pneumonia complicated by severe dyspnea and respiratory failure, consists of symptom reduction, ultimately supported by mechanical ventilation. Patients with severe SARS-CoV-2, a prominent feature of COVID-19, show several similar symptoms to Critical Asthma Syndrome (CAS) patients, such as pulmonary edema, mucus plugging of distal airways, decreased tissue oxygenation, (emergent) exhaustion due to severe dyspnea and respiratory failure. Prior application of elective phosphodiesterase (PDE)3-inhibitors milrinone and enoximone in patients with CAS yielded rapid symptomatic relief and reverted the need for mechanical ventilation, due to their bronchodilator and anti-inflammatory properties. Based on these observations, we hypothesized that enoximone may be beneficial in the treatment of patients with severe SARS-CoV-2 pneumonia and prominent CAS-features. In this case report enoximone was administered to four consecutive patients (1 M; 3 F; 46–70 y) with emergent respiratory failure due to SARS-CoV-2 pneumonia. Clinical outcome was compared with three controls who received standard care only. After an intravenous bolus of enoximone 20 mg followed by 10 mg/h via perfusor, a rapid symptomatic relief was observed: two out of four patients recovered within a few hours, the other two (with comorbid COPD GOLD II/III) responded within 24–36 h. Compared to the controls, in the enoximone-treated patients respiratory failure and further COVID-19-related deterioration was reverted and mechanical ventilation was prevented, leading to reduced hospital/ICU time. Our preliminary observations suggest that early intervention with the selective PDE3-inhibitor enoximone may help to revert respiratory failure as well as avert mechanical ventilation, and reduces ICU/hospital time in patients with severe SARS-CoV-2 pneumonia. Our findings warrant further research on the therapeutic potential of PDE3-inhibition, alone or in combination with other anti-COVID-19 strategies. [ABSTRACT FROM AUTHOR]

Background:Club cell protein (CC16) is a pneumoprotein secreted by epithelial club cells. CC16 possesses anti-inflammatory properties and is a potential biomarker for airway epithelial damage. We studied the effect of inhaled allergen on pulmonary and systemic CC16 levels. Methods:Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Bronchoscopy with bronchoalveolar lavage (BAL) and brushings was performed before and 24 h after the challenge. CC16 was quantified in BAL and CC16 positive cells and CC16 mRNA in bronchial brushings. CC16 was measured in plasma and urine before and repeatedly after the challenge. Thirty subjects performed a mannitol inhalation challenge prior to the allergen challenge. Results:Compared to baseline, CC16 in plasma was significantly increased in all subjects 0–1 h after the allergen challenge, while CC16 in BAL was only increased in subjects without a late allergic response. Levels of CC16 in plasma and in the alveolar fraction of BAL correlated significantly after the challenge. There was no increase in urinary levels of CC16 post-challenge. Mannitol responsiveness was greater in subjects with lower baseline levels of CC16 in plasma. Conclusions:The increase in plasma CC16 following inhaled allergen supports the notion of CC16 as a biomarker of epithelial dysfunction. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease affecting over 300 million people worldwide. The common association with allergic rhinitis and the presence of proinflammatory cells and mediators in the circulation of patients qualify asthma as a systemic disease. This characteristic and the fact that the gold-standard therapy for persistent asthma, inhaled corticosteroids, cannot suppress all components of airway inflammation and fail to adequately penetrate into the small airways, warrant the quest for effective systemic anti-asthma therapies. This review describes the most important controlled studies of montelukast, a once-daily leukotriene receptor antagonist, in asthma and allergic rhinitis in both adults and children. Montelukast is a systemically active drug with a targeted, dual mechanism of action, acting both as a bronchodilator and anti-inflammatory. In patients of all ages, montelukast has shown a favorable safety profile and was well-tolerated. Both as monotherapy or in combination with inhaled corticosteroids, montelukast produced clinically relevant improvements in asthma-related parameters, including symptoms, lung function parameters, quality of life and the number of asthma exacerbations. Furthermore, bronchoprotective effects have been reported both against specific and nonspecific bronchoactive stimuli. Similarly, in patients with allergic rhinitis, montelukast produced substantial improvements in symptoms and quality of life. Long-term studies aimed to determine its effects on airway remodeling are still lacking. INSET: Key issues. [ABSTRACT FROM AUTHOR]