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Other smoking-affected pulmonary diseases.

Cigarette smoking is the leading cause of preventable death in the United States. Smoking adversely affects many organ systems, but especially the lung. Carcinoma of the lung and chronic obstructive pulmonary disease account for most smoking-associated respiratory morbidity and mortality, and their association with smoking is both well established and widely recognized. Cigarette smoking also is associated with differences in the incidence, severity, or natural history of a broad array of other respiratory illnesses, ranging from the common cold to pneumothorax, pulmonary hemorrhage, and various interstitial lung diseases. Interestingly, while the general effect of smoking on respiratory diseases is adverse, in the cases of sarcoidosis and hypersensitivity pneumonitis smoking may actually be associated with a decrease in the incidence of disease. In this article, the author briefly discusses some of the pulmonary and systemic effects of smoking that might mediate its effects on an array of lung diseases, then comprehensively reviews less common or less well-recognized smoking-affected lung diseases such as pulmonary infections, spontaneous pneumothorax, Goodpasture's syndrome, eosinophilic granuloma and other interstitial lung diseases, and pulmonary metastatic disease.

Acyclovir↗

Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine.

The antipicornaviral activity of an ethanolic extract of the green aerial parts of the Australian plant Pterocaulon sphacelatum (Labill.) Benth. & Hook. f. ex F. Muell. has been investigated. This plant has been a favoured traditional medicine, used for the treatment of colds by the Australian Aboriginal people. Antiviral activity-guided fractionation of the extract of P. sphacelatum using an inhibition of poliovirus-induced cytopathic effect assay, has yielded the antiviral flavonoid chrysosplenol C (3,7,3'-trimethoxy-5,6,4'-trihydroxyflavone). This compound is a 4'-hydroxy-3-methoxyflavone, one of a group of compounds known to be potent and specific inhibitors of picornaviral replication. These compounds inhibit the replication of rhinoviruses, the most frequent causative agent of the common cold. The coumarin 6,7,8-trimethoxycoumarin was also isolated from the ethanolic extract.

Antiviral Agents↗

Activation of antiviral protein kinase leads to immunoglobulin E class switching in human B cells.

An epidemiologic association between viral infections and the onset of asthma and allergy has been documented. Also, evidence from animal and human studies has suggested an increase in antigen-specific immunoglobulin E (IgE) production during viral infections, and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provide molecular evidence for the roles of viral infection and of activation of the antiviral protein kinase (PKR) (double-stranded-RNA [dsRNA]-activated protein kinase) in the induction of IgE class switching. The presence of dsRNA, a known component of viral infection and an activator of PKR, induced IgE class switching as detected by the expression of germ line epsilon in the human Ramos B-cell line. Furthermore, dsRNA treatment of Ramos cells resulted in the activation of PKR and in vivo activation of the NF-kappaB complex. Interestingly, infection of Ramos cells with rhinovirus (common cold virus) serotypes 14 and 16 resulted in the induction of germ line epsilon expression. To further evaluate the role of PKR in the viral induction of IgE class switching, we infected Ramos cells with two different vaccinia virus (cowpox virus) strains. Infection with wild-type vaccinia virus failed to induce germ line epsilon expression; however, a deletion mutant of vaccinia virus (VP1080) lacking the PKR-inhibitory polypeptide E3L induced the expression of germ line epsilon. Collectively, the results of our study define a common molecular mechanism underlying the role of viral infections in IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma.

B-Lymphocytes↗

[A case of relapsing Guillain-Barré syndrome following Miller Fisher syndrome].

Miller Fisher syndrome (FS) is thought to be a variant of Gullain-Barré syndrome (GBS), both of which rarely relapse. We report a rare case of GBS that followed FS. A 38-year-old woman had ophthalmoplegia, ataxia and areflexia following an upper respiratory tract infection with a diagnosis of FS. Serum anti-GQ1b IgG antibody was found to be increased, but decreased through immunoadsorption as the neurological symptoms of the patient improved. She became completely asymptomatic three months after the onset of FS. Following a common cold two months later, however, she developed weakness of all four limbs and dysesthesia of hands and feet with albuminocytologic dissociation of cerebrospinal fluid, which was consistent with the diagnosis of GBS. Moreover, serum anti-GQ1b IgG antibody had increased again. Anti-GQ1b IgG antibody frequently becomes positive not only in FS but also GBS with ophthalmoplegia. However, the antibody was positive in this particular patient with GBS, even in the absence of ophthalmoplegia. This case suggests that anti-GQ1b IgG antibody might be a common pathogenesis of both FS and GBS.

Adult↗

[Respiratory infections caused by Branhamella catarrhalis in 5 different hospitals].

During 9 months (from January 1988 to September 1988), we experienced 82 patients (94 episodes) of respiratory infections with Branhamella catarrhalis in 5 different hospitals. There were 11 patients of acute bronchitis, 8 patients of pneumonia, 56 patients of chronic bronchitis (68 episodes), 3 patients of bronchiectasis, 3 patients of bronchial asthma with infection and chronic pulmonary emphysema in one patient. Ten cases of acute bronchitis and 3 cases of pneumonia had a recent history of common cold, with no underlying disease. There were 68 episodes of acute exacerbation of chronic bronchitis, the highest among 94 episodes of all respiratory infection. In chronic bronchitis the single pathogen B. catarrhalis was more than B. catarrhalis associated with other pathogens. H. influenza was associated with B. catarrhalis in in most cases of polymicrobial infection. beta-lactamase producing B. catarrhalis was 71% and oral penicillin was not effective in 8 cases of infection by beta-lactamase producing strains. These results show that B. catarrhalis is very important as a common pathogen of respiratory infection.

Adult↗

Mechanisms of exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation.

Animals↗

Why has antibiotic prescribing for respiratory illness declined in primary care? A longitudinal study using the General Practice Research Database.

BACKGROUND: Antibiotic prescribing by general practitioners (GPs) increased in the 1980s and peaked in 1995. Prescribing volumes subsequently fell by over a quarter between 1995 and 2000, mostly accounted for by reduced antibiotic prescribing for acute respiratory illnesses. We aimed to investigate changes in consultation rates and the proportion of consultations with antibiotics prescribed for different types of respiratory tract infections. METHODS: Data were derived from 108 UK general practices, covering a mean of 642,685 patients, reporting data to the General Practice Research Database (GPRD) continuously between 1994 and 2000. OUTCOME MEASURES: annual age- and sex-standardized consultation rates for 11 different acute respiratory infections per 1000 registered patients and proportions of these consultations resulting in an antibiotic prescription. RESULTS: The standardized consultation rate for 'any respiratory infection' declined by 35 per cent from 422 to 273 per 1000 registered patients, per year. The largest relative reductions in consultation rates were observed for 'common cold' (50 per cent), 'laryngitis' (43 per cent) and 'sore throat' (43 per cent). The standardized proportion of consultations that resulted in an antibiotic prescription for 'any respiratory infection' declined from 79 per cent in 1994 to 67 per cent in 2000. The largest relative reductions in antibiotic prescribing rates occurred in patients recorded as suffering from 'influenza' (52 per cent), 'upper respiratory tract infections' (33 per cent) and 'laryngitis' (30 per cent). Overall, antibiotic prescriptions for all acute respiratory infections declined by 45 per cent. CONCLUSION: The reduction in antibiotic prescribing in common respiratory infections between 1994 and 2000 has occurred partly because GPs are prescribing antibiotics less frequently when patients consult but mainly because there are fewer consultations with these conditions. Further work should aim to understand the reasons for the decline in consultations for respiratory infections and whether further reductions in antibiotic prescribing are feasible.

Acute Disease↗

Atopic sensitization and respiratory symptoms among Polish and Swedish school children.

Allergic sensitization and symptoms from the airways in relation to air pollution were compared in 10-12-year-old school children (n = 1113) from urban Konin in central Poland and both urban and rural parts of Sundsvall in northern Sweden. The measurements included parental questionnaires, skin-prick tests and serial peak flow measurements during 2 weeks with simultaneous monitoring of outdoor air pollutants. The skin-prick test technique was validated by IgE antibody determinations. The levels of common industrial pollutants, SO2 and smoke particles were much higher in Konin than in urban Sundsvall and the levels of NO2 were similar. Various respiratory symptoms were more often reported among school children in Konin (except for wheezing and diagnosed asthma). Multiple logistic regression analyses yielded the following increased odds ratios for children in Konin as compared with the reference group (rural Sundsvall): chest tightness and breathlessness 3.48 (95% confidence interval 2.08-5.82), exercise-induced coughing attacks 3.69 (95% confidence interval 1.68-8.10), recurrent episodes of common cold 2.79 (95% confidence interval 1.53-5.09) and prolonged cough 4.89 (95% confidence interval 2.59-9.23). In contrast, as compared with rural Sundsvall, the adjusted odds ratio for a positive skin-prick test was decreased in Konin, but increased in urban Sundsvall, 0.58 (95% confidence interval 0.37-0.91) and 1.67 (95% confidence interval 1.15-2.42) respectively. The study confirms that living in urban, as compared with rural areas, is associated with an increased prevalence of respiratory symptoms and sensitization to allergens. These differences could be explained by air pollution. Respiratory symptoms were more common in a similar urban group of Polish children who were exposed to even higher levels of air pollution. These children, however, had a much lower prevalence of sensitization to allergens, as compared with the Swedish children. This indicates that differences in lifestyle and standard of living between western Europe and a former socialist country influences the prevalence of atopy.

Air Pollutants↗

Leisure sickness: a pilot study on its prevalence, phenomenology, and background.

AIM: To explore the prevalence, phenomenology, and background of leisure sickness, i.e., the condition of people developing symptoms of sickness during weekends and/or vacations. METHOD: In order to obtain an estimate of its prevalence, a representative Dutch sample consisting of 1,128 men and 765 women was asked to indicate to what extent they recognized themselves in our description of weekend and vacation sickness. For the investigation of the phenomenology and background of this condition and the characteristics of the patients suffering from it, questionnaire data were collected in new samples consisting of 114 cases and 56 controls. Questions referred to symptoms, onset, duration, appreciation of weekend and vacation activities, and appraisal of work and workload. RESULTS: In the case of male respondents, 3.6 and 3.2% recognized themselves in the description of the weekend and the vacation syndrome, respectively, compared with 2.7 and 3.2% women. Most frequently reported symptoms were headache/migraine, fatigue, muscular pains, and nausea. In addition, viral infections (flue-like, common cold) were often reported in relation to vacations. Cases had generally suffered from leisure sickness for over 10 years and the onset was associated with stressful conditions. They attributed their condition to difficulties with the transition from work to nonwork, stress associated with travel and vacation, as well as workload and personality characteristics. There were no significant group differences in the appreciation of weekend and leisure activities or lifestyle during days off. Most striking differences were found with respect to experienced workload, sense of responsibility, and inability to relax. CONCLUSION: Leisure sickness is a relatively common condition. Specific lifestyle factors or leisure activities seem to be less relevant for its development. Concerning risk factors, the data tend to point to high workload and person characteristics, namely, the inability to adapt to the nonworking situation, a high need for achievement, and a high sense of responsibility with respect to work. Future studies should be designed for testing specific hypotheses concerning the underlying mechanisms and evaluating the effectiveness of psychological and/or physical activity interventions.

Adult↗

Rhinovirus and the lower respiratory tract.

Human rhinoviruses (HRVs) are well-recognised causes of common colds and associated upper respiratory tract complications such as sinusitis and otitis media. This article reviews information linking HRV infection to illness in the lower respiratory tract. HRVs are capable of efficient replication in vitro at temperatures present in the tracheobronchial tree and have been shown to cause productive infection, elaboration of cytokines and chemokines, and up-regulation of cell surface markers in human bronchial epithelial cells. In situ hybridisation studies have proven that HRV infection occurs in the tracheobronchial tree following experimental infection. Clinical studies report that HRV infection is the second most frequently recognised agent associated with pneumonia and bronchiolitis in infants and young children and commonly causes exacerbations of pre-existing airways disease in those with asthma, chronic obstructive pulmonary disease or cystic fibrosis. HRV infection is associated with one-third to one-half of asthma exacerbations depending on age and is linked to asthma hospitalisations in both adults and children. Limited information implicates HRV infection as a cause of severe lower respiratory tract illness in older adults and in highly immunocompromised hosts, particularly bone marrow transplant recipients. More information is needed about the pathogenesis of HRV infection with regard to lower respiratory tract complications in these diverse patient groups. Given the large unmet medical need associated with HRV infections, safe and effective antiviral agents are needed for both prevention and treatment of these infections.

Adolescent↗

Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat.

Kinins are generated in nasal secretions during allergic reactions and during induced rhinovirus colds. To determine if kinins may contribute to the symptomatology of these inflammatory reactions, 8 subjects were challenged with increasing doses of bradykinin or with placebo. Levels of albumin, histamine, and N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase were measured in nasal lavages, and symptom scores were noted. No symptoms or increases in mediators or protein were observed after placebo challenge. Symptom scores increased in a dose-dependent manner, however, in response to bradykinin challenge. Increased symptoms were associated with significant increases in albumin and TAME-esterase activity, but no increases in histamine were observed. Nasal conductance measurements confirmed that bradykinin induces dose-dependent unilateral obstruction in the challenged nostril. Other common symptoms were rhinorrhea and, of particular relevance to rhinovirus infections, a persistent sore throat. We conclude that bradykinin causes increased vascular permeability and rhinitis, which are independent of mast cell mediator release. Kinins may, therefore, contribute to the symptomatology of inflammatory reactions of the upper airways, including the common cold.

Adult↗

Episodic viral wheeze in preschool children: effect of topical nasal corticosteroid prophylaxis.

BACKGROUND: The effect of prophylactic nasal corticosteroids on wheezing episodes associated with colds was investigated in a 12 week parallel group, double blind, randomised controlled trial in preschool children. METHODS: Data were collected from 50 children aged 12-54 months with a history of at least three episodes of wheeze associated with colds over the previous winter, but few or no interval symptoms; 24 were given one dose of fluticasone aqueous nasal spray (50 micro g) into each nostril twice daily and 26 received an indistinguishable placebo spray. Episodes of lower respiratory illness occurring within 2 days of the onset of a cold were identified from daily symptom diaries. The main outcome was nocturnal symptom score during the first 7 days of an episode. RESULTS: The groups were well balanced on entry except that the treatment group had a history of more prolonged episodes. During the trial there was no significant difference in the number of episodes in the treatment and control groups (27 and 37, respectively), in the severity of nocturnal symptoms (mean score 1.33 and 1.22, respectively, confidence interval of difference -0.24 to +0.47) or in daytime symptoms, activity or total scores during episodes. Compliance was estimated to be over 50% in 43 of the children. CONCLUSIONS: Nasal corticosteroid treatment does not prevent acute wheezy episodes associated with upper respiratory infections (common colds) in preschool children.

Administration, Intranasal↗

Rhinovirus infection of human embryonic lung fibroblasts induces the production of a chemoattractant for polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMNLs) appear in the nasal mucosa during rhinovirus colds before the onset of symptoms. This study describes a chemoattractant for PMNLs that is elaborated by human embryonic lung fibroblast cells infected with rhinovirus. Chemotaxis assays were done in a 48-well microchemotaxis chamber with normal adult PMNLs. Medium supernatants from rhinovirus-infected cell culture attracted 87 +/- 6 (mean +/- SE) PMNLs/10 high-power fields (x450) compared with 38 +/- 6 PMNLs/10 high-power fields attracted by medium from uninfected cell cultures (P less than .0001). Elaboration of the chemoattractant was not a result of cell destruction and did not require the presence of infectious virus. This chemoattractant produced by human fibroblast cells may contribute to the influx of PMNLs into the nasal mucosa during rhinovirus infection. The PMNLs may, in turn, have a role in producing symptoms of the common cold.

Cells, Cultured↗

Interaction of coxsackievirus A21 with its cellular receptor, ICAM-1.

Coxsackievirus A21 (CAV21), like human rhinoviruses (HRVs), is a causative agent of the common cold. It uses the same cellular receptor, intercellular adhesion molecule 1 (ICAM-1), as does the major group of HRVs; unlike HRVs, however, it is stable at acid pH. The cryoelectron microscopy (cryoEM) image reconstruction of CAV21 is consistent with the highly homologous crystal structure of poliovirus 1; like other enteroviruses and HRVs, CAV21 has a canyon-like depression around each of the 12 fivefold vertices. A cryoEM reconstruction of CAV21 complexed with ICAM-1 shows all five domains of the extracellular component of ICAM-1. The known atomic structure of the ICAM-1 amino-terminal domains D1 and D2 has been fitted into the cryoEM density of the complex. The site of ICAM-1 binding within the canyon of CAV21 overlaps the site of receptor recognition utilized by rhinoviruses and polioviruses. Interactions within this common region may be essential for triggering viral destabilization after attachment to susceptible cells.

Amino Acid Sequence↗

Respiratory viruses detected in hospitalised paediatric patients with respiratory infections.

Over 200 strains of respiratory viruses cause a variety of human infections ranging from common cold to life-threatening pneumonia. Respiratory viruses implicated in this study are respiratory syncytial viruses (RSV), adenovirus, influenza viruses and parainfluenza viruses. The objective of this study is to determine the epidemiology of respiratory viruses in paediatric patients with lower respiratory tract infection. The methods used were direct antigen detection method, shell vial culture method and conventional tube culture method. The samples included in this study are paediatric patients seen in Universiti Kebangsaan Malaysia Hospital, Kuala Lumpur with suspected acute viral respiratory infection, presenting with acute laryngotracheobronchitis (croup), bronchiolitis and pneumonia. Nasopharyngeal aspirates were collected and processed almost immediately. A total of 222 specimens were received during February 1999 to January 2000 showing a dual peak pattern in the months of April and December. The mean age of the patients was 13 months. Pneumonia (77.9%) was the most common clinical diagnosis in children with lower respiratory tract infection. This was followed by bronchiolitis (19.4%) and croup (27%). Viral aetiologies were confirmed in 23.4% of the patients. The most common respiratory virus isolated or detected was RSV, followed by parainfluenza viruses, influenza viruses and adenovirus.

Bronchiolitis, Viral↗

The sore throat. When to investigate and when to prescribe.

Sore throats are most commonly due to infections, many of which are viral and do not require specific treatment. Symptoms and signs of the common cold, influenza or croup, the occurrence of conjunctivitis in some adenoviral infections, generalised lymphadenopathy and splenomegaly in glandular fever or the presence of vesicles characteristic of herpangina (Coxsackie A virus) or of herpes simplex infection, occasionally enable a clinical diagnosis and avoid the need for antibiotic therapy. In the case of treatable conditions a typical membrane may suggest diphtheria, a scarlatiniform rash infection due to Streptococcus pyogenes or to Corynebacterium haemolyticum, and a cherry-red epiglottis Haemophilus influenzae type b. Associated atypical pneumonia suggests infection with Mycoplasma pneumoniae or Chlamydia pneumoniae. Pharyngitis due to Neisseria gonorrhoeae may be accompanied by infection at other sites or by other sexually transmitted diseases. Candidal infection, in the appropriate clinical circumstance, should suggest HIV infection. Surgical drainage is required in the case of peritonsillar or retropharyngeal abscess. Noninfectious cases of sore throat, e.g. thyroiditis, are relatively uncommon considerations in the differential diagnosis of acute febrile pharyngitis. The most common problem is to recognise streptococcal pharyngitis, which requires antibiotic treatment for 10 days to avoid the risk of rheumatic fever.

Humans↗

Headache caused by drinking cold water is common and related to active migraine.

The primary aim of this study was to estimate the prevalence of cold-induced headache and to test if it is associated with migraine. Women attending a population-based mammography screening programme were asked to participate in the study. Fifty-one of 669 women (7.6%) experienced a headache after ingesting 150 ml of ice-cold water through a straw. Women who had experienced one or more migraine attacks in the last year (active migraine) were twice as likely to experience a headache from ingesting the cold water as women who had never suffered from migraine. Ninety-five women who had experienced their most recent migraine attack more than 1 year ago (inactive migraine) were not at increased risk. The prevalence of active and inactive migraine was 19.4 and 14.2%, respectively. Headache caused by drinking cold water is common in women. The results indicate that active migraine facilitates the perception of forehead pain induced by a cold palatal stimulus.

Adult↗

The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses.

BACKGROUND: Coxsackievirus A9 (CAV9), a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-stranded RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. One of the four capsid proteins, VP1, includes the arginine-glycine-aspartate (RGD) motif within its C-terminal extension. This region binds to integrin alpha v beta 3, the only receptor for CAV9 to be conclusively identified to date. RESULTS: The crystal structure of CAV9 in complex with the antiviral compound WIN 51711 has been solved to 2.9 A resolution. The structures of the four capsid proteins, VP1 to VP4, resemble those of other picornaviruses. The antiviral compound is bound in the VP1 hydrophobic pocket, and it is possible that the pocket entrance contains a second WIN 51711 molecule. Continuous electron density for the VP1 N terminus provides a complete picture of the structure close to the fivefold axis. The VP1 C-terminal portion is on the outer surface of the virus and becomes disordered five-residues N-terminal to the RGD motif. CONCLUSIONS: The RGD motif is exposed and flexible in common with other known integrin ligands. Although CAV9 resembles coxsackie B viruses (CBVs), several substitutions in the areas implicated in CBV receptor attachment suggest it may recognise a different receptor. The structure along the fivefold axis provides new information on the uncoating mechanism of enteroviruses. CAV9 might bind a larger natural pocket factor than other picornaviruses, an observation of particular relevance to the design of new antiviral compounds.

Amino Acid Sequence↗