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There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID‐19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID‐19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS‐CoV‐2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti‐inflammatory and mucolytic properties that may be useful in this context. Methods and intervention: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID‐19 Requiring invasive ventilation Meta‐Trial (CHARTER‐MT) is a collaborative prospective individual patient data analysis of on‐going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID‐19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID‐19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo‐controlled studies) while under invasive ventilation. Each participating study collect a pre‐defined minimum dataset. The primary outcome for the meta‐trial is the number of ventilator‐free days up to day 28 day, defined as days alive and free from invasive ventilation. [ABSTRACT FROM AUTHOR]

The emerging recognition that chronic obstructive pulmonary disease (COPD) is a complex disorder, characterized not only by local pulmonary inflammation, but also by systemic inflammation that might have an adverse impact on various extrapulmonary organs, such as the blood vessels and the heart, among others, emphasizes the need for new and more effective forms of therapy for this debilitating disorder. Fortunately, many of the 'standard' therapeutic options used to treat COPD have the potential to influence systemic inflammation. Moreover, several new therapeutic strategies aimed at controlling the underlying inflammatory processes of COPD more specifically are under development. Unfortunately, we still do not know whether treatment of lung inflammation decreases, for example, the risk of acute cardiac events, progression of atherosclerosis or thrombotic events. It is also unclear whether, alternatively, treatment of heart disease can affect the progression of lung disease. Nonetheless, initial data seem to indicate that drugs, such as statins, ACE inhibitors, AT1 receptor blockers and PPAR agonists, used to treat a co-morbid condition have the potential to benefit COPD patients.

Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and naive, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites. edema; lipopolysaccharide; lung inflammation; magnetic resonance imaging

Cough is an indispensable defensive reflex. Although generally beneficial, cough is also a common symptom of diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Cough remains a major unmet medical need and, although the centrally acting opioids have remained the antitussive drug of choice for decades, such opioids possess many unwanted side-effects. However, new research into the behaviour of airway sensory nerves has provided greater insight into the mechanisms of cough and new avenues for the discovery of novel non-opioid antitussive drugs. In this article, the pathophysiological mechanisms of cough and the implications of this research for the development of novel antitussive drugs will be discussed. A poster depicting the pharmacology of cough is available online and in print as supplementary material to this article.

As the prevalence of resistance to multiple antibiotics increases it is progressively more difficult to treat pneumonia in hospitalized patients. Therefore, anti-infectious agents that have new modes of action are needed urgently. Recent advances in DNA sequencing technology make it possible to elucidate the sequences of the entire genomes of pathogenic bacteria. This allows many novel, non-traditional targets for therapeutic intervention to be identified, such as those involved in disease pathogenesis, and in adaptation and growth at sites of infection. In the past few years, inhibitors of new bacterial targets have been developed, including inhibitors of genes that are required for either virulence or pathogenesis. The challenge is to optimize and develop these agents to provide novel approaches to the treatment of pneumonia in hospitalized patients.

Asthma is a major medical problem but, despite decades of research, the mechanisms that underlie this condition remain elusive. Although the eosinophil has been regarded as a cell that is central to the pathogenesis of asthma, the failure to abrogate asthma symptoms by novel treatments that are designed to suppress the recruitment of eosinophils to the airways challenges this dogma. Our approach to understanding bronchial asthma needs to be broadened to include alterations in the function of afferent nerves that supply airways. Changes in the activity of these nerves offer a possible mechanism by which asthmatic subjects are uniquely responsive to a wide range of physiological and chemical stimuli. Here, we review the current status of asthma research.