Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nontuberculous mycobacteria (NTM) are increasingly associated with pulmonary disease. This is a worldwide phenomenon and one that is not related just to better diagnostic techniques or HIV infection. The mode of transmission of NTM is not well defined, but environmental exposure may be the major factor. While most exposed and infected individuals never acquire NTM disease, some ostensibly immunocompetent persons will. Although our understanding of the pathogenesis of NTM disease is incomplete, we believe that both host and mycobacterial factors are involved. Among the former, interferon-gamma"trafficking" may well play a central role. When disease occurs, it is likely to present in one of three prototypical forms: a tuberculosis-like pattern often affecting older male smokers with COPD; nodular bronchiectasis classically occurring in middle-aged or older women who never smoked and present with cough; and hypersensitivity pneumonitis following environmental exposure. While Mycobacterium avium complex has been described with all three forms, many other NTM can produce one or another of them; variants of these prototypes also exist. Diagnosis of NTM disease relies on microbiology and chest CT scanning, and criteria to aid diagnosis are available. Treatment of disease depends on the species involved, extent and form of disease, and overall condition of the patient. Surgery for localized disease may be useful for those species expected to be refractory to medical therapy. Observation without treatment may be appropriate for some patients with slowly progressive disease that is expected to be particularly difficult to treat.
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PMID:Pulmonary disease due to nontuberculous mycobacteria. 1884 28

The mechanisms of bronchial secretion are an important part of the innate defense system that protects the airways against pathogens and environmental toxins. Bronchial secretions are mainly produced by goblet cells and submucosal glands but also small amounts of surfactant from clara cells and some other fluids are part of the airway epithelium fluid. Together with the ciliary system the bronchial secretions are essential for the bronchial clearance ("mucociliary clearance"). Cilia beat within a periciliary layer with low viscosity ("sol-phase"). They move the overlying mucous sheet ("gel-phase") by their tips towards the nose to remove those mucous particles together with foreign material and pathogens from the airways. The gel-layer of the airway epithelium fluid is formed mainly by water, mucins (MUC) and free proteins. Mucins are highly glycosylated macromolecules, to date more than 18 different MUC-genes have been described. In addition the airway epithelium fluids contains many antibacterial proteins and peptides including lysozyme, lactoferrin, secretory IgA, complement, beta-defensines as well as many others. Acute inflammatory or toxic stimuli can promote hypersecretion of mucins mediated by a large variety of cytokines and chemokines or even directly like some toxins. Chronic inflammatory conditions like asthma or COPD are associated with hyperplasia of goblet cells and submucosal glands thus increasing the secretory capacity of the airways. The system of mucociliary clearance forms a functional unit together with the coughing mechanisms discussed elsewhere in this journal.
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PMID:[Physiology and pathophysiology of bronchial secretion]. 1831 75

Dogs have been extensively used to model the important components of asthma and COPD. Many of the key features of human asthma such as reversible airflow obstruction, pulmonary inflammation, airway hyperresponsiveness and cough are demonstrated in dogs after provocation with antigen, following a period of hyperventilation with dry air or after inhalation of ozone. Furthermore, standard anti-asthma drugs such as beta-adrenergic agonists, corticosteroids and leukotriene inhibitors are effective in these models. The pathology and pathophysiology of chronic bronchitis and emphysema can also be demonstrated in dogs after exposure to cigarette smoke, following inhalation of sulfur dioxide and by intra-tracheal or aerosol administration of proteolytic enzymes such as papain. These canine models of COPD have been used to evaluate a variety of new methodologies and treatments before they are tested in humans. This review highlights some of the important features of these canine models and how they have increased our understanding of the pathology, pathophysiology and control of human asthma and COPD.
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PMID:Canine models of asthma and COPD. 1832 32

Although cough and sputum production may impact patients' well being and functioning in COPD and chronic bronchitis, there is no validated instrument for cough and sputum symptoms and their impact on patients' daily activities. To fill that gap, we developed and validated a specific, multilingual Cough and Sputum Assessment Questionnaire (CASA-Q) that evaluates clinical symptoms and their impact on patients with COPD or chronic bronchitis. In a three-country validation study (n=671), there was adequate internal consistency (Cronbach's alphas, 0.80-0.91) and test-retest reliability (correlation coefficients>0.70) for the CASA-Q. The cough impact and sputum impact domains correlated with the SGRQ impact domain and SGRQ total score, as did the cough impact domain with the SF-36 social functioning domain. The cough symptom and sputum symptom domains correlated with sputum wet weight (p<0.05; r=-0.56), but not with cough recordings. The mean CASA-Q cough symptom and sputum symptom domain scores indicated responsiveness towards both worse and improved symptoms, whereas the impact domains scored already in the upper third of the scale range, indicating the need for further improvement of its properties. Differences in the CASA-Q domain scores by smoking status (current vs. former smokers) were highest for cough symptoms and lowest for sputum impact. These data indicate that the CASA-Q may be a useful measure of cough and sputum production, and their impact in patients with COPD and/or chronic bronchitis. Further validation will need to assess the responsiveness of the CASA-Q to changes in symptoms.
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PMID:Development and validation of a cough and sputum assessment questionnaire. 1866 68

A 76-year-old man was admitted with acute exacerbation of COPD. He was administered bronchodilators, antibiotics and oral corticosteroids. Although his cough, sputum, fever and the laboratory data improved. wheezing and dyspnea remained. The chest CT revealed severe stenosis of the trachea and both main bronchi, which was thought to be the cause of the symptoms, and similar to the condition of "excessive dynamic airway collapse (EDAC)". We treated him with NPPV and his symptoms improved and he returned home. "EDAC"-like tracheobronchial stenosis with COPD treated with NPPV is rare.
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PMID:[A case of severe COPD associated with tracheo-bronchial stenosis, treated with non-invasive positive pressure ventilation]. 1906 66

After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing, shortness of breath, sore throat and dry mouth. Physical exercise increases the transport of inhaled insulin into the circulation and in consequence the likelihood of hypoglycemia. Other problems were the inability to deliver precise insulin doses, because the smallest blister pack available contained the equivalent of 3 U of regular insulin and this dose would make it difficult for many people using insulin to achieve accurate control, which is the real goal of any insulin therapy. For example, someone on 60 U of insulin per day would lower the blood glucose about 90 mg/dl (5 mmol) per 3 U pack, while someone on 30 U a day would drop 180 mg/dl (10 mmol) per pack. Precise control was not possible, especially compared with an insulin pump that can deliver one twentieth of a unit with precision. Another disadvantage was the size of the device. The Exubera inhaler, when closed, was about the size of a 200 ml water glass. It opened to about twice the size for delivery. To our information also other companies (Eli Lilly in cooperation with ALKERMES, Novo Nordisk (AERx, Liquid), Andaris (Powder)) stopped further development and it is unclear whether an inhaled form of insulin will ever be marketed, because of the problems that have occurred. Only Mannkind (Technosphere, Powder) is still working on a Phase III trial. However, our review will briefly summarize the experience regarding inhalant administration of insulin and will describe potential future developments for this type of therapy focussing on the lung.
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PMID:Inhaled insulin--does it become reality? 1921 34

To determine if a delay in presentation to the emergency department (ED) after the onset of symptoms of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of hospital admission. A prospective cohort study utilizing data from 396 patient visits to 29 North American EDs. Inclusion criteria were age > or = 55 years; a diagnosis of COPD; and presentation for treatment of AECOPD, as defined by increasing shortness of breath, worsening cough, or change in sputum production at presentation. The median age was 69 years and 54% were female. Most patients (70%) presented to the ED > 24 hours after symptom onset, and most (61%) were hospitalized. On multivariate logistic regression analysis, after adjusting for 12 potential confounders (including demographics, clinical features, other diagnoses, and bronchodilator use before arrival), a delay in presentation > or = 24 hours was associated with a over two-fold increase in the odds of admission (odds ratio = 2.2, 95% confidence interval 1.1-4.8). This increase in risk persisted for delay in presentation > or = 12 hours in place of 24 hours, after restricting the analysis to patients admitted outside the intensive care unit, and to those reporting the ED as their usual site of care. A majority of patients delay presentation to the ED for > or = 24 hours after symptom onset, and are at higher risk of hospitalization. Early presentation should be emphasized to patients and caregivers to advance efforts to decrease the morbidity, mortality, and costs of AECOPD treatment.
COPD 2009 Apr
PMID:Acute exacerbations of COPD: delay in presentation and the risk of hospitalization. 1937 18

Bronchiectasis is a heterogeneous disorder with a large number of etiologic factors. The main symptom is a chronic productive cough. The aim of this study was to describe the phenotypes of patients with bronchiectasis who had developed a chronic productive cough in childhood (before 16 years of age) compared with those who had developed a productive cough as adults. One hundred and eighty-two subjects with bronchiectasis diagnosed by computed tomography scanning were studied. Subjects all had a detailed clinical review and assessment of potential etiologic factors performed by the investigators. There were 107 (59%) subjects who developed a chronic productive cough in childhood and 75 (41%) subjects who developed a chronic productive cough in adulthood. There were significant differences in a number of parameters between the two groups including duration of cough, frequency of exacerbations, presence of rhinosinusitis, crackles on examination and lung function. The adult group could be further divided into those who had developed a cough whilst smoking and those who had no obvious relationship with smoking. In conclusion there were a number of significant differences between the child onset and adult onset group that may reflect different phenotypes of bronchiectasis.
COPD 2009 Apr
PMID:Phenotypes of adult bronchiectasis: onset of productive cough in childhood and adulthood. 1937 26

Acute cough is a major symptom of viral respiratory tract infection and causes excessive morbidity in human populations across the world. A wide variety of viruses play a role in the development of cough after acute infection and all of these manifest a similar clinical picture across different age groups. Despite the large disease burden surprisingly little is known about the mechanism of acute cough following viral infection. Both in vitro and in vivo experiments show that increased production of neuropeptides and leukotrienes mediate cough after viral infection, along with altered expression of neural receptors. Increased airway mucus production is also likely to play a significant role. This work is reviewed in this article. Following the recent development of a mouse model for rhinovirus infection and the establishment of experimental models of rhinovirus challenge in human subjects with both asthma and COPD the field is expanding to translate in vitro research into clinical studies and hopefully eventually into clinical practice. Developing a clearer understanding of the mechanisms underlying virus induced cough may lead to more specific and effective therapies.
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PMID:Cough and viruses in airways disease: mechanisms. 1948 62

Cigarette smoking has been causally linked several diseases, primarily lung cancer and chronic obstructive lung disease (COPD). The diagnosis of COPD currently involves an assessment of smoking and/or occupational exposures, a history of cough, sputum and dyspnea and spirometric measures of airflow obstruction and since spirometric measures take long follow up times to detect significant changes, surrogate measures of outcome capable of predicting long-term health changes have been sought for. These include biomarkers of oxidative stress, inflammation and tissue damage in sputum, bronchoalveolar lavage, exhaled breath and serum. Published biomarker studies have not always accurately compared patients with COPD with age-matched cigarette smokers and non-smoking normal subjects without significant airflow limitation, also comparable for other exposures. Consequently, the interpretation of biomarker association studies is somewhat difficult. The purpose of this narrative review is to summarize publications reporting cellular, soluble or volatile marker of obstructive lung disease in populations of healthy non-smokers and healthy smokers, in order to determine whether the biomarkers examined could be specifically associated with exposure to tobacco smoke rather than with inflammation and airway hyper-reactivity. As induced sputum has been the most widely used investigative tool, this review has been aimed at assessing induced sputum biomarkers, referring to lung biopsy, bronchoalveolar lavage and exhaled breath markers as supporting evidence for biomarkers associations identified with induced sputum studies.
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PMID:Biomarkers of lung damage associated with tobacco smoke in induced sputum. 1960 95


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