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Plasma levels of von Willebrand factor antigen in acute bronchitis and in a normal population.

von Willebrand factor (vWF) is a large glycoprotein secreted predominantly by endothelial cells in both the systemic and pulmonary circulations and has a central role in the formation of the platelet plug. It has been put forward as a possible marker of endothelial cell injury, but is not ideal in that it is not specific for either the pulmonary or systemic circulation and may be released as part of the acute phase response from otherwise healthy endothelial cells. We undertook two studies (i) to assess within-subject to assess within-subject variation in plasma von Willebrand factor antigen (vWF:Ag) levels over time and to assess between-subject variation in a healthy patient population, and (ii) as part of a descriptive study of acute bronchitis, to assess whether plasma vWF:Ag levels altered in such a common and minor insult. A random sample of patients aged 45-74 years were taken from a local general practice. vWF:Ag levels were measured on three occasions, and spirometry was performed. The descriptive study was undertaken on patients in the general practice diagnosed with acute bronchitis without pre-existing pulmonary disease. Plasma vWF:Ag was measured on presentation and 14 and 42 days later. In 219 randomly selected patients the mean plasma vWF:Ag was similar at all three visits, the within-subject standard deviation being 0.09 U ml(-1) and 1.12 U ml(-1) respectively). There was no correlation between plasma vWF:Ag and C-reactive protein on presentation. We conclude that there is relatively little variation in an individual's plasma vWF:Ag level but that levels increase significantly with age. The observed elevation occurring with acute bronchitis is a true phenomenon; the absence of an associated acute phase response suggests that endothelial cell injury is the mechanism for the rise. These observations are important in the context of vWF as a marker of endothelial cell damage, as a common and supposedly minor insult such as acute bronchitis may markedly raise plasma levels.

Acute Disease↗

Increasing prevalence of asthma but not of chronic bronchitis in Finland? Report from the FinEsS-Helsinki Study.

To assess the prevalence of asthma, chronic bronchitis and respiratory symptoms, and to calculate risk factors for them, we performed a postal survey in Helsinki, the capital of Finland. During the spring of 1996, questionnaires were mailed to a random sample of 8000 individuals aged 20-69. The total response rate was 76%, with 6062 complete answers. The prevalence of having ever had asthma was 7.2%, physician-diagnosed asthma was 6.6% and physician-diagnosed chronic bronchitis was 3.7%. Asthma was significantly more common among women than men, but no gender differences existed in prevalence of chronic bronchitis. The most common respiratory symptom was sputum production when coughing, reported by 27%. During the previous 12 months, wheezing had occurred in 20% and attacks of shortness of breath in 13% of subjects. Generally, the prevalence of different respiratory symptoms were significantly higher among smokers. The most important risk factor for asthma was a family history of asthma (Odds ratio:OR 3.3). Multivariate analysis revealed that being a member of the socioeconomic group, manual workers, was associated with a significantly increased risk for chronic productive cough (OR 1.7), and for wheezing during the previous 12 months (OR 1.7). Manual workers of both genders had the highest prevalence of asthma, chronic productive cough and wheezing during the previous 12 months. The prevalence of asthma in Helsinki was higher than previously found in Finland, and was at a similar level to that of other Nordic countries. In contrast, prevalence of chronic bronchitis was lower than previously shown in Finland.

Adult↗

[Risk factors for increased cost of exacerbations of chronic bronchitis and chronic obstructive pulmonary disease].

OBJECTIVE: To identify what variables characterizing the patients, exacerbations, and treatment of chronic bronchitis and chronic obstructive pulmonary disease (COPD) are associated with a higher direct health cost. METHOD: Observational pharmacoeconomic study of exacerbations of chronic bronchitis and COPD (of probable bacterial etiology, defined as Anthonisen types I or II). Direct health costs were assessed during 30 days of follow-up. Logistic regression was employed for statistical analysis, with calculation of the adjusted odds ratios (OR). An exacerbation cost greater than 150 euros was defined as the dependent variable. RESULTS: Data on 1164 patients were collected by 252 physicians. Pharmacoeconomic data were complete in 947 patients (82.6%). In the first 30 days, 206 sought medical attention because of unsatisfactory response to treatment (21.8%), 69 (7.3%) attended the emergency room, and 22 (2.3%) were admitted to hospital. Overall, 101 exacerbations (10.7%) were classified as high cost (> 150 euros). Continuous oxygen therapy (OR = 7.58) and previous hospitalization (OR = 2.6) were associated with high-cost exacerbations, whereas diagnosis of chronic bronchitis (OR = 0.41) and treatment of the exacerbation with moxifloxacin or amoxicillin-clavulanic acid as opposed to clarithromycin (OR = 0.38) were associated with low-cost exacerbations. CONCLUSION: Treatment failure was reported for 21.8% of the patients with exacerbations of chronic bronchitis and COPD. Repeated medical visits and requests for complementary tests were the main factors responsible for increased cost. Variables associated with high-cost exacerbations were continuous oxygen therapy, previous hospitalization, and treatment with clarithromycin as opposed to moxifloxacin or amoxicillin-clavulanic acid.

Aged↗

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.

Administration, Oral↗

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.

Administration, Inhalation↗

The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review.

The role of N-acetylcysteine (NAC) in the treatment of chronic bronchitis is unclear. Since a number of studies have been published on this topic, a systematic review of published studies seems justified. A systematic search (Medline, Embase, Cochrane Library, bibliographies, no language restriction) for published randomized trials comparing oral NAC with placebo in patients with chronic bronchitis was performed. Dichotomous data on prevention of exacerbation, improvement of symptoms and adverse effects were extracted from original reports. The relative benefit and number-needed-to-treat were calculated for both individual trials and combined data. Thirty-nine trials were retrieved; eleven (2,011 analysed patients), published 1976-1994, were regarded as relevant and valid according to preset criteria. In nine studies, 351 of 723 (48.5%) patients receiving NAC had no exacerbation compared with 229 of 733 (31.2%) patients receiving placebo (relative benefit 1.56 (95% confidence interval (CI) 1.37-1.77), number-needed-to-treat 5.8 (95% CI 4.5-8.1). There was no evidence of any effect of study period (12-24 weeks) or cumulative dose of NAC on efficacy. In five trials, 286 of 466 (61.4%) patients receiving NAC reported improvement of their symptoms compared with 160 of 462 (34.6%) patients receiving placebo (relative benefit 1.78 (95% CI 1.54-2.05), number-needed-to-treat 3.7 (95% CI 3.0-4.9)). With NAC, 68 of 666 (10.2%) patients reported gastrointestinal adverse effects compared with 73 of 671 (10.9%) taking placebo. With NAC, 79 of 1,207 (6.5%) patients withdrew from the study due to adverse effects, compared with 87 of 1,234 (7.1%) receiving placebo. In conclusion, with treatment periods of approximately 12-24 weeks, oral N-acetylcysteine reduces the risk of exacerbations and improves symptoms in patients with chronic bronchitis compared with placebo, without increasing the risk of adverse effects. Whether this benefit is sufficient to justify the routine and long-term use of N-acetylcysteine in all patients with chronic bronchitis should be addressed in further studies and cost-effectiveness analyses.

Acetylcysteine↗

Airway nitric oxide in infants with acute wheezy bronchitis.

Concentrations of nitric oxide (NO) in exhaled air are increased in children and adults with asthma, and NO measurements are used as a non-invasive marker to monitor airway inflammation in these patients. To define the role of NO in infants with acute wheezy bronchitis, we measured nasal and end-tidal NO concentrations in 17 infants with acute virus-associated wheezy bronchitis, in 22 term infants without respiratory disease, and in nine premature infants. Nasal NO measurements were performed with an olive placed in the infant's nose; end-tidal NO concentrations were assessed during tidal breathing through a snuggly fitting face mask. Both end-tidal NO concentrations and nasal NO concentrations were reduced in infants with acute wheezy bronchitis. There were no differences in NO concentrations between term infants and premature infants. Measurements by both techniques were highly reproducible, as assessed by repeated measurements three times daily on three consecutive days in eight premature infants. Reduced airway NO concentrations in infants with virus-associated acute wheezy bronchitis are in contrast to findings in adults where both upper and lower airway NO levels are increased in patients with asthma. Whether this reflects a different inflammatory reaction to upper airway infections in acutely wheezy infants or pathophysiologic differences in airway response remains to be determined.

Acute Disease↗

The excess cost of acute exacerbations of chronic bronchitis in patients aged 45 and older in England and Wales.

INTRODUCTION: Chronic Bronchitis is a serious and costly health problem. Prevalence is estimated at 45 per 10,000 persons in the United Kingdom. Approximately 120,000 Pounds would be saved for every 100 hospital admissions avoided. A reduction in acute exacerbations of chronic bronchitis (AECB), treatment failures, and subsequent hospital admission could have a significant impact on the burden of AECB borne by secondary care facilities in the UK National Health Service (NHS). OBJECTIVE: The aim of this study is to provide an economic assessment of the direct cost to the health care system associated with the management of chronic bronchitis and its acute exacerbations. DESIGN: A prevalence-based, excess-cost-of-illness analysis is undertaken from the perspective of the UK NHS. Disease prevalence data, primary health care resource utilization, hospital inpatient and outpatient resource utilization, and costs of health care were taken from a variety of data sources, including a large UK national survey of general practice (GP) consultations, the General Practice Research Database, a survey from a single NHS hospital trust, and the national health-care resource and cost statistics. RESULTS: From 1994 to 1995, approximately 233,000 cases of chronic bronchitis were detected in the persons aged 45 and older in the United Kingdom. Prevalence peaked at 204 per 10,000 in the group of subjects aged 75 to 84 years. During that same period, the total excess cost of primary care associated with AECB was calculated at 35.7 million Pounds. The largest component of primary care costs was the excess cost of all prescription medicines, which totaled 27.8 million Pounds. The excess cost attributed to antibacterial and respiratory prescription medications alone was estimated at 9 million Pounds. Excess costs attributed to GP consultations and hospital emergency room visits were 6.5 million Pounds and 1.3 million Pounds, respectively. The excess costs arising from inpatient hospital episodes included 8.3 million Pounds for hospital admissions, 660,000 Pounds for outpatient costs, and 225,000 Pounds for day care. CONCLUSIONS: These results suggest that improving the management of AECB with the objective of reducing the number of AECB treatment failures and the associated hospital admissions could significantly reduce expenditures by the UK NHS.

Aged↗

Eosinophilic bronchitis as a cause of chronic cough.

Eosinophilic bronchitis is a recently described condition in patients with chronic cough, sputum eosinophilia, normal spirometry and no evidence of bronchial hyperreactivity. The aim of the study was to assess the causes of chronic cough and to identify the prevalence of eosinophilic bronchitis as a cause of chronic cough. Thirty-six patients [mean age 45.4 +/- 14.3 years (range 16-69 years), M/F: 4/32] with an isolated chronic cough lasting for more than 4 weeks were recruited from the outpatient clinic. In all patients, after a full history and physical examination, blood eosinophil count, eosinophilic cationic protein (ECP), serum total and specific IgE levels were measured. Spirometry, methacholine provocation test, skin prick tests, ear, nose and throat examination, induction of sputum and esophageal pH testing were performed. The mean duration of cough was 31.3 +/- 52.3 months. Sputum eosinophilia greater than 3% was present in 12 (33.3%) patients and they were diagnosed as eosinophilic bronchitis. Their induced sputum had a mean eosinophil count of 8.3% and a mean ECP level of 98.5 mg x l(-1), which were higher than the others (P=0.003, both). The diagnosis of the remaining patients were postnasal drip syndrome in eight, gastroesophageal reflux disease in eight, post-infectious cough in two and cough-variant asthma in one patient. In conclusion, eosinophilic bronchitis is an important cause of chronic cough and should be considered in the assessment of patients before regarding them as having idiopathic chronic cough.

Adolescent↗

Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants.

Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.

Adolescent↗

In vitro susceptibility patterns of nonserotypable Haemophilus influenzae from patients with chronic bronchitis.

The antimicrobial susceptibility patterns of 76 nonserotypable Haemophilus influenzae (biotypes I-IV) from patients with chronic bronchitis were compared against ten orally administered antimicrobial agents. In addition the sputum ampicillin concentrations one hour after standard therapy were determined in five patients with chronic bronchitis. Ampicillin resistance was demonstrated in one strain (biotype IV) which produced beta-lactamase and two strains (biotype II) with innate resistance (MIC = 4 mg/l). Resistance to trimethoprim, chloramphenicol, ciprofloxacin and cefaclor was not detected. The incidence of resistance to tetracycline was 0.5% and cephalexin 13.2%. A high incidence of resistance to erythromycin (95%) was noted. There was no association between resistance and biotype of nonserotypable H. influenzae. The sputum ampicillin concentrations from four out of five patients given standard antibiotic doses were shown to be sufficient to inhibit the growth of the majority of nonserotypable H. influenzae strains one hour after treatment. This study shows that the incidence of nonserotypable H. influenzae resistant to ampicillin is low in this community but that resistance levels to erythromycin, commonly prescribed for the management of acute bronchitis, are high. Regular sensitivity screens are important in monitoring the value of various antibiotic regimens in the management of acute bronchitis.

Administration, Oral↗

Retrospective evidence that the MHC (B haplotype) of chickens influences genetic resistance to attenuated infectious bronchitis vaccine strains in chickens.

Infectious bronchitis is a respiratory disease of chickens that is caused by the coronavirus infectious bronchitis virus (IBV). Virtually all broiler and layer breeder flocks are routinely vaccinated against IBV. Two hatches of 1-day-old chicks from four lines were mistakenly vaccinated for infectious bronchitis using a moderately attenuated vaccine designed for chicks of an older age. The vaccination resulted in high mortality, and chicks from three of four lines died with signs typical of infectious bronchitis. The mortality that occurred using this less-attenuated vaccine was significantly influenced by the genetic line, and the MHC (B) haplotype in chickens of three B congenic lines. B congenic chickens possessing the B*15 haplotype were resistant in contrast to chickens possessing the B*13 or B*21 haplotypes. Chicks from two further hatches of the four lines were vaccinated appropriately with a more attenuated IBV vaccine, and only limited chick mortality was seen. These retrospective data from two repeated hatches confirm earlier data indicating chicken genes influence resistance to IBV, and indicate for the first time that genes tightly linked to the B haplotype are relevant in resistance to IBV. Due to extenuating circumstances it was not possible to verify results with chicks from F2 matings. Factors that may enhance definition of the role of the B haplotype in immune response to IBV, and the desirability for further analysis of a B haplotype-linked influence on immunity to IBV are discussed.

Animals↗

Urban air particulate inhalation alters pulmonary function and induces pulmonary inflammation in a rodent model of chronic bronchitis.

Epidemiological studies have reported increased morbidity in human populations following inhalation of elevated levels of urban particulate matter. These responses are especially prevalent in populations with chronic obstructive pulmonary diseases, including chronic bronchitis. Toxicological studies have reported altered pulmonary function and increased pulmonary inflammation following particulate inhalation in the laboratory setting. However, most of these studies have utilized artificial particles that may not accurately mimic outdoor air pollutant conditions. Few studies have utilized actual urban air particle samples in inhalation studies. In the present study, the effects of inhaled concentrated urban air particulates on pulmonary function and pulmonary inflammation are addressed. Normal rats and rats with chronic bronchitis induced by approximately 200 ppm SO(2) for 6 wk were subsequently subjected to filtered air or concentrated air particles (CAPs). Twelve rats per group in 4 groups (48 rats total) were exposed for 5 h/day for 3 consecutive days. The CAPs aerosol levels were 206, 733, and 607 microg/m(3) (MMAD = 0.18 microm, sigma(g) = 2.9) on days 1, 2, and 3, respectively. Following the final day of exposure, pulmonary function parameters, including peak expiratory flow (PEF), tidal volume (TV), respiratory frequency (RF), and minute volume (MV), were measured and compared to preexposure baseline levels. Twenty-four hours following the final day of exposure, bronchoalveolar lavage was performed for total cell counts, differential cell counts, and total lavage protein levels. Pulmonary responses to CAPs in chronic bronchitic animals indicated a significant increase in tidal volume as well as peak expiratory flow. In CAPs-exposed animals without underlying bronchitis, significantly increased tidal volume was observed. Significant pulmonary inflammation was observed in the CAPs-exposed animals, particularly those with chronic bronchitis. Significant increases in neutrophils, lymphocytes, and total lavage protein were observed. These results suggest two distinct mechanistic responses to inhaled particles: a stress-type pulmonary function response marked by increases in flow and volume, that is, deeper breathing; and acute pulmonary inflammation marked by cellular influx, particularly neutrophils. From these data it is concluded that inhaled urban air particles alter pulmonary breathing parameters and increase pulmonary inflammation.

Air Pollutants↗

A survey of chronic bronchitis among brassware workers.

A stratified random sample of 580 workers aged between 18 and 50 years representing each sub-occupation in the brassware industry was studied for the prevalence of chronic bronchitis in relation to occupational and environmental factors. The findings were compared with those obtained in a reference group (N = 131) belonging to similar socio-economic status and unexposed to a dusty environment. Although the exposed group showed higher prevalence of chronic bronchitis in comparison to that observed in the controls (10.5 vs 5.3%), the difference was not significant at the 5% level. It was observed that the workers engaged in non-dusty occupations such as brass sheet cutting and engraving showed the lowest prevalence of the disease (5.0%) while those engaged in the dusty occupations viz., casting, soldering, electroplating and polishing showed the highest prevalence (12.0%). The smoking adjusted odds ratios calculated in various sub-occupations showed the highest risk of developing chronic bronchitis among the polishers (2.74). Though the risk in other occupational sub-groups was double, it did not attain a level of significance. The smoking adjusted odds ratios in relation to length of exposure showed that the risk was significantly higher among the workers exposed for over 10 years compared to those who worked for less than 10 years in the grinding, soldering and brass ingot making operations. The study thus showed a dose-response relationship between length of exposure and chronic bronchitis while effect of age on the disease was not discernible probably due to the small number of cases and the young age of the study group. The concentration of various metals in the air samples drawn from the work environment where main processes were in operation, was low compared to the prescribed level by ACGIH.

Adolescent↗

Air pollution involving nitrogen dioxide exposure and wheezing bronchitis in children.

BACKGROUND: A population-based case-control study was performed in Stockholm to assess the influence of air pollution on the occurrence of severe wheezing bronchitis in children. METHODS: The study included 197 children aged 4 months to 4 years, who were hospitalized because of breathing difficulties with wheezing, and 350 population controls. Information on potential risk factors for childhood wheezing and a residential history was obtained at home interview with parents. Outdoor nitrogen dioxide (NO2) concentrations at home addresses and day care centres from birth on were estimated from validated models, mainly using data on traffic intensity from municipal registers. RESULTS: The risk of wheezing bronchitis was related to time-weighted mean outdoor NO2 exposure in girls (P = 0.02), but not in boys. A gas stove in the home appeared to be a risk factor primarily for girls. All analyses controlled for parental asthma and maternal smoking, which were independent risk factors for wheezing bronchitis. CONCLUSIONS: The results suggest that exposure to combustion products containing NO2 may be of particular importance for the development of wheezing bronchitis in girls.

Air Pollutants↗

Infectious exacerbations of chronic bronchitis: diagnosis and management.

Chronic bronchitis is an increasing cause of significant morbidity and mortality. Despite treatment, respiratory tract infection is the most common identifiable cause of death for patients with chronic obstructive pulmonary disease. Repeated infectious exacerbations may ultimately cause acute and chronic lung injury. The most common bacterial aetiologies of acute exacerbations of chronic bronchitis (AECB) include Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Pseudomonas aeruginosa is often a nosocomial pathogen and is becoming more prevalent in patients with severe underlying disease. Viruses are responsible for approximately one-third of acute exacerbations overall. Atypical pathogens are causative pathogens in < 10% of episodes. The diagnosis of AECB is often based on clinical impression, although suspicion of bacterial infection can be enhanced by quantitative Gram's stains from appropriately obtained sputum specimens. However, a specific microbiological diagnosis is only needed in certain specific situations. Management of AECB involves non-drug interventions (e.g. smoking cessation) and antibiotic treatment. Recommendations for antibiotic use in patients with known or highly suspected AECB are still evolving. The selection of an antibiotic for treatment of an infectious episode must consider underlying patient co-morbidities, likely pathogens, resistance issues and individual antibiotic properties. Cephalosporins, beta-lactam/beta-lactamase inhibitor combinations and macrolides are all reasonable choices. However, due to the increasing prevalence of resistance to standard antibiotics among common respiratory pathogens, and increased incidence of Pseudomonas spp., fluoroquinolones should be a first-line treatment for AECB in patients who have chronic bronchitis complicated by co-morbid illness, severe obstruction (FEV1 < 50%), old age (> 65 years) or have recurrent exacerbations. In patients who do not have these risk factors (i.e. those with simple chronic bronchitis), agents such as co-trimoxazole remain useful.

Bacterial Infections↗

Variable pulmonary responses from exposure to concentrated ambient air particles in a rat model of bronchitis.

Chronic bronchitis may be considered a risk factor in particulate matter (PM)-induced morbidity. We hypothesized that a rat model of human bronchitis would be more susceptible to the pulmonary effects of concentrated ambient particles (CAPs) from Research Triangle Park, NC. Bronchitis was induced in male Sprague-Dawley rats (90-100 days of age) by exposure to 200 ppm sulfur dioxide (SO2), 6 h/day x 5 days/week x 6 weeks. One day following the last SO2 exposure, both healthy (air-exposed) and bronchitic (SO2-exposed) rats were exposed to filtered air (three healthy; four bronchitic) or CAPs (five healthy; four bronchitic) by whole-body inhalation, 6 h/day x 2 or 3 days. Pulmonary injury was determined either immediately (0h) or 18 h following final CAPs exposure. The study protocol involving 0 h time point was repeated four times (study #A, November, 1997; #B, February, 1998; #C and #D, May, 1998), whereas the study protocol involving 18 h time point was done only once (#F). In an additional study (#E), rats were exposed to residual oil fly ash (ROFA), approximately 1 mg/ m(3)x6 h/day x 3 days to mimic the CAPs protocol (February, 1998). The rats allowed 18 h recovery following CAPs exposure (#F) did not depict any CAPs-related differences in bronchoalveolar lavage fluid (BALF) injury markers. Of the four CAPs studies conducted (0 h time point), the first (#A) study (approximately 650 microg/m3 CAPs) revealed significant changes in the lungs of CAPs-exposed bronchitic rats compared to the clean air controls. These rats had increased BALF protein, albumin, N-acetyl glutaminidase (NAG) activity and neutrophils. The second (#B) study (approximately 475 microg/m3 CAPs) did not reveal any significant effects of CAPs on BALF parameters. Study protocols #C (approximately 869 microg/m3 CAPs) and #D (approximately 907 microg/m3 CAPs) revealed only moderate increases in the above mentioned BALF parameters in bronchitic rats exposed to CAPs. Pulmonary histologic evaluation of studies #A, #C, #D, and #F revealed marginally higher congestion and perivascular cellularity in CAPs-exposed bronchitic rats. Healthy and bronchitic rats exposed to ROFA (approximately 1 mg/m3) did not show significant pulmonary injury (#E). Analysis of leachable elemental components of CAPs revealed the presence of sulfur, zinc, manganese, and iron. There was an apparent lack of association between pulmonary injury and CAPs concentration, or its leachable sulfate or elemental content. In summary, real-time atmospheric PM may result in pulmonary injury, particularly in susceptible models. However, the variability observed in pulmonary responses to CAPs emphasizes the need to conduct repeated studies, perhaps in relation to the season, as composition of CAPs may vary. Additionally, potential variability in pathology of induced bronchitis or other lung disease may decrease the ability to distinguish toxic injury due to PM.

Acetylglucosaminidase↗

Parental smoking, urinary cotinine, and wheezing bronchitis in children.

We conducted a case-control study to assess the role of exposure to environmental tobacco smoke (ETS) in the development of wheezing bronchitis in children. The study included 199 children age 4 months to 4 years, who were treated in hospital for wheezing bronchitis, and 351 population controls of the same age group. We estimated exposure to ETS from urinary cotinine measurements as well as from questionnaires to parents. The median urinary cotinine concentration was 5.7 micrograms per liter in cases and 4.4 micrograms per liter in controls. Breast-feeding was related to urinary cotinine excretion in children with smoking mothers. The risk of wheezing bronchitis increased in relation to parental smoking and urinary cotinine concentration. This effect was most prominent in children up to 18 months of age, among whom the relative risk was 3.3 in those with a urinary cotinine level exceeding 20 micrograms per liter (95% confidence interval = 1.5-7.6). Our data confirm that ETS is an important risk factor for wheezing bronchitis in children and indicate that a single urinary cotinine measurement offers no major advantages to questionnaire data for assessment of long-term exposure to ETS.

Breast Feeding↗