Asthma is one of the most common conditions seen in clinical practice and carries both a significant disease burden in terms of patient morbidity and a high economic burden in both direct and indirect costs. Despite this, it remains a comparatively poorly understood disease, with only modest advances in treatment over the past decade. Corticosteroids remain the cornerstone of therapy. Both patient compliance with medications and physician adherence to evidence-based guidelines are often poor, and a high percentage of patients continue to have inadequately controlled disease even with optimal therapy. Following a contextual overview of the current treatment guidelines, this review focuses on novel asthma therapies, beginning with the introduction of the leukotriene receptor antagonist zafirlukast in the 1990s, continuing through advanced endoscopic therapy and into cytokine-directed biologic agents currently in development. Along with clinically relevant biochemistry and pharmacology, the evidence supporting the place of these therapies in current guidelines will be highlighted along with data comparing these agents with more conventional treatment. A brief discussion of other drugs, such as those developed for unrelated conditions and subsequently examined as potential asthma therapies, is included.
BackgroundEosinophilic COPD phenotype is associated with greater airway remodelling, exacerbation risk, and steroid responsiveness. However, little is known about the prevalence and characteristics of pulmonary hypertension (PH) in this patient population.MethodsWe retrospectively evaluated a cohort of COPD patients with right heart catheterisation (RHC) data at a university hospital between January 2011 and May 2019 and compared the pulmonary vascular profile and prevalence of PH between eosinophilic and non-eosinophilic patients using a definition of eosinophilic COPD as at least 3 blood eosinophil values ≥300 cells·µL−1. We used multivariable logistic regression analyses to examine the association between eosinophilic COPD and various PH categories adjusting for age, sex, body mass index, forced expiratory volume (%) in 1 s, smoking status, and use of supplemental oxygen.ResultsAmong 106 COPD patients with RHC data and at least three blood eosinophil values, 25% met the definition of eosinophilic COPD. Fewer patients amongst the eosinophilic group required long term oxygen therapy (69% versus 93%, p=0.001) and total lung capacity was significantly lower in the eosinophilic group (p=0.006). This group had higher mPAP (median, (IQR); 30, (27–41) versus 25, (22–30) mmHg, p=0.001) and pulmonary vascular resistance (PVR) (4, (2.8–5.1) versus 2.9, (2.1–4.1) WU, p=0.018). On multivariable logistic regression analyses, eosinophilic phenotype was associated with PH (aOR=6.5 (1.4–30.7), p=0.018), pre-capillary PH (aOR=3.2 (1.1–9), p=0.027) but not severe PH (aOR=2.1 (0.6–7.2), p=0.219).ConclusionEosinophilic COPD was associated with higher mPAP, PVR and with increased likelihood of PH. More studies are needed to further explore this finding.
INTRODUCTION:The advent of corona virus disease as a global health emergency has resulted in the trial of several empiric pharmacological regimens, many of which are associated with deleterious adverse effects. However, because of the lack of viable treatments and rapidity of spread, physicians around the world have used them in an attempt to improve survival in critically ill patients. One such drug is Tocilizumab, which was hypothesized to have a role in managing the cytokine release syndrome ("Cytokine storm") associated with this illness. We report our experience with 2 critically ill patients with COVID-19 who received Tocilizumab and subsequently developed intestinal perforation. CASE PRESENTATION: Patient A was a 74-year-old gentleman with COVID-19 pneumonia whose hospitalization was complicated by development of adynamic ileus presumed secondary to sepsis, that was conservatively managed. Due to worsening tachypnea, tachycardia and higher oxygen requirements, he was given Tocilizumab. 2 weeks into his hospital stay, his surveillance imaging demonstrated small bowel perforation with free intraperitoneal air and intrabdominal abscesses. He was started on antibiotics, total parenteral nutrition and obtained 2 intraperitoneal drains. His further hospital stay was complicated by development of hypotension and asystole cardiac arrest. Patient B was a 65-year-old renal transplant recipient with COVID-19 pneumonia who received Remdesivir, Dexamethasone, convalescent plasma and Tocilizumab. During his hospital stay, he had worsening hypoxic respiratory failure requiring mechanical ventilation. Subsequently, patient developed fevers with worsening leukocytosis and new pressor requirements. He was started on broad spectrum antibiotic coverage and imaging demonstrated pneumatosis of ascending colon concerning for impending perforation. After discussion with family members, patient was transitioned towards comfort measures. DISCUSSION: Tocilizumab is an Interleukin-6 receptor antagonist which was used for the profound inflammatory state associated with COVID-19. Recent studies have demonstrated its ineffectiveness in preventing further clinical deterioration, intubation or death in moderately ill hospitalized patients with COVID-19. In prior studies in rheumatoid arthritis, Tocilizumab was noted to have a higher incidence of lower gastrointestinal perforations, especially with preexisting diverticulitis or steroid use. The exact mechanism of bowel perforation is unclear and is likely multifactorial. Early after bowel injury, there is a substantial increase in Interleukin-6 expression that stimulates epithelial proliferation. Absence of this, in combination with intestinal hypoperfusion seen in critically ill patients may potentially increase the risk of intestinal perforation. Our cases emphasize the importance of close monitoring and caution while using lesser known and more risky medications without clearly established guidelines.
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