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Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population. We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19. Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary artery disease (26%), and chronic obstructive pulmonary disease (14%). Twenty patients had severe COVID-19 (34.5%) and 38 had nonsevere disease (65.5%). Severe disease was more common in older SOT recipients with comorbidities and was associated with cough, dyspnea, pneumonia, C-reactive protein >10 mg/L, and platelet count <150/μL. Sex, race, body mass index, time from transplant, baseline immunosuppression, and diagnosis month did not differ among those with severe and nonsevere COVID-19. Seventy percent of SOT recipients were hospitalized vs 27.2% of general patients with COVID-19 and inpatient SOT recipients had a higher mechanical ventilation rate. Though a trend toward longer length of stay, higher intensive care unit admission, and greater inpatient mortality was observed (19.5% vs 14.8%), these differences were not significant. The severe acute respiratory syndrome coronavirus 2 has greatly impacted SOT recipients. One-third of our SOT recipients seen during the first wave had severe illness with associated standard risk factors for poor outcome. Compared with general first-wave patients, more SOT recipients were hospitalized, although inpatient COVID-19 mortality did not significantly differ. [ABSTRACT FROM AUTHOR]

This review provides an assessment of post-inhalation cough with therapeutic aerosols. Factors that increase cough may be mitigated through design of the drug, formulation, and device. The incidence of cough is typically less than 5% for drugs with a nominal dose less than 1 mg, including asthma and COPD therapeutics. Cough increases markedly as the dose approaches 100 mg. This is due to changes in the composition of epithelial lining fluid (e.g., increases in osmolality, proton concentration). Whether an individual exhibits cough depends on their degree of sensitization to mechanical and chemical stimuli. Hypersensitivity is increased when the drug, formulation or disease result in increases in lung inflammation. Cough related to changes in epithelial lining fluid composition can be limited by using insoluble neutral forms of drugs and excipients. Unlabelled Image [ABSTRACT FROM AUTHOR]

• Cough is a defense mechanism for clearing the airways but may become troublesome. • Chronic cough of known and unknown cause(s) frequently requires medical attention. • Chronic cough of known cause(s) must be treated according to guidelines. • Chronic refractory cough may benefit from neuromodulatory/speech pathology therapy. • Novel promising neuromodulatory agents are in clinical development. Cough, a defense mechanism for clearing the airways of secretions, exudate, or foreign bodies, may become a troublesome symptom. Chronic cough, one of the most frequent symptoms requiring medical attention, is often not due to identifiable causes in adults. Chronic productive cough defines chronic bronchitis, and thus is present in 100% of these patients, and frequently in patients with bronchiectasis, cystic fibrosis, and chronic infectious respiratory diseases. However, chronic cough is most frequently dry. Thus, chronic cough in adults is a difficult syndrome requiring multidisciplinary approaches, particularly to diagnose and treat the most frequent identifiable causes, but also to decide which patients may benefit by treating the central cough hypersensitivity by neuromodulatory therapy and/or non-pharmacologic treatment (speech pathology therapy). Recent guidelines provide algorithms for diagnosis and assessment of cough severity; particularly chronic cough in adults. After excluding life-threatening diseases, chronic cough due to identifiable causes (triggers and/or diseases), particularly smoking and/or the most frequent diseases (asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic bronchitis, and adverse reactions to drugs [angiotensin-converting enzyme inhibitors and sitagliptin]) should be treated by avoiding triggers and/or according to guidelines for each underlying disease. In patients with troublesome chronic cough due to unknown causes or persisting even after adequate avoidance of triggers, and/or treatment of the underlying disease(s), a symptomatic approach with neuromodulators and/or speech pathology therapy should be considered. Additional novel promising neuromodulatory agents in clinical development (e.g., P2X3 inhibitors) will hopefully become available in the near future. [ABSTRACT FROM AUTHOR]

Highlights • Cough is a cardinal symptom in COPD and increases during exacerbation. • Cough and sputum production are associated with adverse outcomes in COPD. • Smoking, inflammation, neurogenic factors and comorbidities impact cough in COPD. • Detection of increased cough frequency may prove a useful predictor of exacerbation. Abstract Chronic obstructive pulmonary disease is predicted to become the 4th leading cause of death worldwide by 2030. The natural history of the disease includes progressive symptoms punctuated by acute exacerbations during which symptoms rapidly deteriorate. The resulting disability places significant burden on health and social care systems. Cough is the second most common symptom reported by COPD patients, is a source of significant distress and is associated with adverse outcomes. We discuss the importance of cough in COPD, its mechanism and the relationship between cough and COPD exacerbations. We review the literature and present original data relating to the investigation of cough during COPD exacerbation, its associations and potential benefits of cough monitoring. [ABSTRACT FROM AUTHOR]

Tracheobronchomalacia (TBM) is dynamic collapse of the trachea and bilateral mainstem bronchi leading to dyspnea, cough, and recurrent pneumonias. TBM is reported in 10-15% of patients with chronic obstructive pulmonary disease (COPD). Patients with TBM and COPD are not candidates for lung transplant, as TBM will still result in dynamic obstruction of the new allografts. A 70 year old male patient was diagnosed with COPD in 2012 and started on oxygen in 2019. He had worsening dyspnea with a chronic cough, presenting for lung transplant evaluation in 2022. His chest CT showed partial collapse of the right upper lobe, prompting a bronchoscopy notable for severe TBM (Figure 1A). His sputum culture was positive for stenotrophomonas and strep. pneumoniae, which were treated with antibiotics. He was listed for bilateral lung transplant with plan for concurrent tracheobronchoplasty (TBP). Once a suitable allograft was accepted, he was placed in left lateral decubitus position and a right posterolateral thoracotomy was used for the TBP with prolene mesh, which extended from proximal trachea to the mid bilateral mainstem bronchi. Next, the right pneumonectomy and lung transplant was performed with the bronchial anastomosis just distal to the end of the mesh. The thoracotomy was closed, and the patient was placed supine. The left lung transplant was performed via a left anterolateral thoracotomy. The initial P/F ratio was 532 mmHg. He was extubated on postoperative day (POD) 1, and on room air on POD 2. He was discharged on POD 13. A follow up bronchoscopy at 1 month showed resolution of his prior TBM (Figure 1B) with patent bilateral anastomoses. This report is the first known case of combined TBM and lung transplant. For patients with end-stage COPD and TBM, a combined TPS and bilateral lung transplant is technically feasible and safe. [ABSTRACT FROM AUTHOR]

COPD is a disease manifested as persistent airflow obstruction with an enhanced inflammatory response in the airways and lungs to noxious particles and gases which evokes symptoms of dyspnea on exertion, cough and mucus production. Airway smooth muscle plays a central role in the COPD diathesis and is implicated in many aspects of COPD pathogenesis. Vitamin D deficiency has been associated with COPD severity and studies suggest a role for Vitamin D as a treatment for COPD. In this review, we describe the effects of 1,25-dihydroxyvitamin D on airway smooth muscle function, including agonist-induced shortening, secretion of inflammatory mediators, and myocyte hypertrophy and hyperplasia. [Copyright &y& Elsevier]

Abstract: The mammalian transient receptor potential (TRP) superfamily of cation channels is divided into six subfamilies based on sequence homology TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin) and TRPML (mucolipin). The expression of these channels is especially abundant in sensory nerves, and there is increasing evidence demonstrating their existence in a broad range of cell types which are thought to play a key role in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). These ion channels can be activated by a diverse range of chemical and physical stimuli. Physical stimuli include temperature, membrane potential changes and osmotic stress, and some of the more well known chemical stimuli include capsaicin (TRPV1), menthol (TRPM8) and acrolein (TRPA1). There is increasing evidence in this rapidly moving field to suggest that selective blockers of these channels may represent attractive novel strategies to treat characteristic features of respiratory diseases such as asthma and COPD. This review focuses on summarising the evidence that modulation of selected TRP channels may have beneficial effects at targeting key features of these respiratory diseases including airways inflammation, airways hyper-reactivity, mucus secretion and cough. [Copyright &y& Elsevier]

Abstract: To cough is a protective defence mechanism that is vital to remove foreign material and secretions from the airways and which in the normal state serves its function appropriately. Modulation of the cough reflex pathway in disease can lead to inappropriate chronic coughing and an augmented cough response. Chronic cough is a symptom that can present in conjunction with a number of diseases including chronic obstructive pulmonary disease (COPD) and asthma, although often the cause of chronic cough may be unknown. As current treatments for cough have proved to exhibit little efficacy and are largely ineffective, there is a need to develop novel, efficacious and safe antitussive therapies. The underlying mechanisms of the cough reflex are complex and involve a network of events, which are not fully understood. It is accepted that the cough reflex is initiated following activation of airway sensory nerves. Therefore, in the hope of identifying novel antitussives, much research has focused on understanding the neural mechanisms of cough provocation. Experimentally this has been undertaken using chemical or mechanical tussive stimuli in conjunction with animal models of cough and clinical cough assessments. This review will discuss the neural mechanisms involved in the cough, changes that occur under pathophysiological conditions and and how current research may lead to novel therapeutic opportunities for the treatment of cough. [Copyright &y& Elsevier]

Abstract: Eosinophilic airway inflammation may be encountered in asthma and in non asthmatic eosinophilic bronchitis, which is a recently identified and common cause of chronic cough. Non asthmatic eosinophilic bronchitis may be differentiated from asthma by the absence of airflow limitation and of bronchial hyperreactiveness (potentially reflecting the different localization of mast cells within the airway wall). Diagnosis is based on the confirmation of eosinophilic airway inflammation, usually by induced sputum, in the absence of other causes of chronic cough or of radiological and lung function abnormality. The cough is generally improved by inhaled corticosteroids. The long-term outcome is still not known; non asthmatic eosinophilic bronchitis may lead to the onset of fixed airway obstruction or asthma. [Copyright &y& Elsevier]

Abstract: Wood-related work has been recognized during the past thirty years as a source of respiratory diseases. The prevalence of occupational asthma has been estimated to be between 5 and 15% of all asthma, but its frequency is difficult to evaluate because it is underestimated. Indeed, there is no simple, specific diagnostic test, and monitoring of workers is difficult. The pathophysiology of these reactions is diverse and has not been elucidated for certain types of wood. The case that will be presented illustrates the importance of early diagnosis of occupational asthma. It was possible as a result of teamwork between the occupational physician, the respiratory specialist/allergist and the attending physician. [Copyright &y& Elsevier]

Abstract: We review studies of the effects of low ambient ozone concentrations on morbidity that found a negative coefficient for ozone concentration. We call this a Paradoxical Ozone Association (POA). All studies were in regions with methyl ether in gasoline. All but one study carefully controlled for the effects of other criterion pollutants, so the phenomenon cannot be attributed to them. One was in southern California in mid-summer when ozone levels are highest. Because ozone is created by sunlight, the most plausible explanation for a POA would be an ambient pollutant that is rapidly destroyed by sunlight, such as methyl nitrite (MN). A previously published model of engine exhaust chemistry suggested methyl ether in the fuel will create MN in the exhaust. MN is known to be highly toxic, and closely related alkyl nitrites are known to induce respiratory sensitivity in humans. Support for the interpretation comes from many studies, including three linking asthma symptoms to methyl tertiary butyl ether (MTBE) and the observation that a POA has not been seen in regions without ether in gasoline. We also note that studies in southern California show a historical trend from more significant to less significant ozone-health associations. The timing of those changes is consistent with the known timing of the introduction of gasoline oxygenated with MTBE in that region. [Copyright &y& Elsevier]

Abstract: Neurokinin3 (NK3) receptors may regulate the airways primarily through actions on the nerves. In the periphery, airway parasympathetic ganglia neurons are depolarized following NK3 receptor activation resulting subsequently in the facilitation of synaptic transmission. Such an effect may account for the excessive parasympathetic reflex effects (e.g. airway smooth muscle contraction, vascular engorgement, mucus secretion) associated with asthma and chronic obstructive pulmonary disease (COPD). In the central nervous system (CNS), NK3 receptor activation may regulate airway vagal afferent relay neurons, rendering them hyperresponsive to parallel inputs from glutamate containing afferent nerves. This process is analogous to the process of central sensitization regulating hyperalgesia and pain in somatic tissues. In both the CNS and in the airways, NK3 receptors are likely activated by either substance P and/or neurokinin A (NKA), both of which are full agonists at NK3 receptors, as there is little evidence that airway nerves express neurokinin B (NKB). Evidence for other potential sites of regulation by NK3 receptors in the airways (e.g. vasculature, airway smooth muscle, epithelium, mucus glands) is either inconclusive or conflicting. [Copyright &y& Elsevier]

Abstract: In order to determine the feasibility of inhalative vaccination with polysaccharide antigen in patients with chronic obstructive pulmonary disease (COPD), we used controlled inhalation of a defined dose of Pneumovax® in a randomized 3-arm study. The vaccine was either deposited in the alveoli (alveolar vaccination) or in the large airways (bronchial vaccination) and these were compared to standard intramuscular vaccination. Adverse effects were minor and never exceeded WHO grade 2. There was frequent cough, headache and shivering in the bronchial vaccination group, frequent fatigue only in the alveolar vaccination group and no frequent adverse effects in the intramuscular vaccination group. Specific serum IgG antibody was measured before and at 4 and 12 weeks after vaccination. At 12 weeks there was a greater than twofold rise in 7 out of 10 individuals in every vaccination group. Mean antibody levels of responders at 12 weeks were 278mg/l for alveolar vaccination, 238mg/l for bronchial vaccination and 737mg/l for standard intramuscular vaccination. The data show that polysaccharide vaccine can be safely administered by controlled inhalation in COPD patients and that it can induce a rapid serum antibody response. [Copyright &y& Elsevier]

Abstract: The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases. [Copyright &y& Elsevier]

Sensory nerves in the airways regulate central and local reflex events such as bronchoconstriction, airway plasma leakage, mucus secretion and cough. Sensory nerve activity can be enhanced during inflammation and, as a result, these protective reflexes become exacerbated and deleterious. The development of drugs that directly inhibit sensory nerve function has again become an attractive target for the pharmaceutical industry. In particular, the focus is on inhibition of the symptoms associated with airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease and cough of any aetiology. [Copyright &y& Elsevier]

Abstract: Findings by other authors indicate that exposure to chemical emissions from indoor paint is related to asthma symptoms in adults. In their first years of life children are receptive to obstructive airway diseases. The aim of this study was to investigate the influence of redecoration of the apartment on airway symptoms in infants during the first two years of life. The Leipzig Allergy Risk Children Study (LARS) is a birth cohort study with the following inclusion criteria: double positive family atopy anamnesis, cord blood IgE>0.9 kU/l, or low birth weight between 1500 – 2500 g. Within the context of LARS, 186 parents of risk children completed a questionnaire on the respiratory symptoms of their children and the redecoration of their apartment at the end of the first and second year of life. A total 22% of the children suffered from obstructive bronchitis once or more during their first year, and 11% experienced this condition during their second year of life. Redecoration of the apartment had a significant influence on the appearance of obstructive bronchitis in the first (OR 4.1 95%CI 1.4 – 11.9) and in the second year of life (OR 4.2 95%CI 1.4 – 12.9). (The OR are adjusted for cord blood-IgE >0.9 kU/l, birth weight ≤2500 g, male sex and double positive parental atopy anamnesis, dampness, smoking or pet in the apartment). Simultaneous contamination from redecoration activities and additional exposures such as smoking, a pet or dampness in the apartment increased the risk for obstructive bronchitis in the first year (OR 9.1; 95% CI 2.3 – 34.8) as well as in the second year (OR 5.1; 95%CI 1.6 – 15.6). Our data suggest that redecoration of the apartment is associated with the development of acute inflammations, but not with a chronic influence on the airways in atopy risk infants. At an exposure to more than one environmental factor, pronounced effects were seen. [Copyright &y& Elsevier]

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Although the main risk factor is smoking, 15–19% of COPD even in smokers has been attributed to occupational exposures. The aim of this study was to investigate the association between occupational exposure and risk of COPD. Methods: Participants were part of a cross-sectional study of risk factors for COPD. A total of 1232 completed a detailed respiratory questionnaire, spirometric testing and measurement of gas transfer. Job histories were coded according to the International Standard Classification of Occupations. These codes were then used to establish occupational exposures using the ALOHA job exposure matrix. Results: The prevalence of emphysema was 2.4%, chronic obstructive bronchitis 1.8%, and COPD 3.4%. Subjects ever exposed to biological dusts had an increased risk of chronic obstructive bronchitis (OR 3.19; 95% CI 1.27–7.97), emphysema (OR 3.18; 95% CI 1.41–7.13), and COPD (OR 2.70, 95% CI 1.39–5.23). These risks were higher in women than in men. For biological dust, the risk of emphysema and COPD was also significantly increased in both the duration of exposure categories, again in women but not in men. No significant increased risks for COPD were found for mineral dust (OR 1.13; 95% CI 0.57–2.27) or gases/fumes (OR 1.63; 95% CI 0.83–3.22). Conclusion: In this general population sample of adults, occupational exposures to biological dusts were associated with an increased risk of COPD which was higher in women. Preventive strategies should be aimed at reducing exposure to these agents in the workplace. Reproduced with permission from the BMJ Publishing Group. [Copyright &y& Elsevier]