Host inflammatory responses to first isolation of Pseudomonas aeruginosa from sputum in cystic fibrosis

Pseudomonas aeruginosa infection of the respiratory tract in patients with cystic fibrosis is a major determinant of morbidity and mortality. However, it has been postulated that the earliest phase of colonization is not associated with injury. To test this hypothesis we determined the association of the first recorded isolation of P. aeruginosa from the sputum on circulating markers of the inflammatory response in 6 patients with cystic fibrosis. At this time circulating C-reactive protein was increased in all 6 and neutrophil elastase α₁-antitrypsin complex (elastasecomplex) was increased in 5 patients compared with healthy controls. This inflammatory response was associated with a reduction in the FEV, and FVC of all patients [FEV, 1.42 ± 0.87 L (mean ± SD) at first isolation vs. 2.08 ± 0.74 L before isolation; P < 0.05; FVC, 1.94 ± 0.93 L vs. 2.87 ±1.01 L, P < 0,05]. At a median interval of 10 months, 5 patients had raised titres of positive IgG antibody to P. aeruginosa, indicating significant exposure to this organism. At this time, lung function had returned to preinfection levels, whilst 3 patients showed continuing features of an inflammatory response, and the group mean value for elastase-complex was raised. Our findings demonstrate that at the time of first isolation of P. aeruginosa from the sputum of patients with cystic fibrosis, there is a concomitant systemic host response and an acute deterioration of pulmonary function. © 1993 Wiley-Liss, Inc.     

Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis.

The aim of this study was to assess the prognostic significance of mucoid and non-mucoid isolates of Pseudomonas aeruginosa (muPs and non-muPs) from the sputa of patients with cystic fibrosis (CF). Eighty-one children with CF who coughed up sputum daily were recruited and followed over 12 months with frequent sputum cultures. At the end of this observation period they were classified to one of three age-matched groups. In 50 mPs was isolated on one or more occasions; 19 grew non-muPs but not muPs, and 12 grew no isolates of Ps aeruginosa. These 81 children and adolescents were followed for a further 8 years or until they died. Twenty-one (42%) of the muPs patients died compared with two (11%) of the non-muPs and one (8%) of the no Ps patients (P less than 0.01). Stepwise regression indicated that forced expiratory volume in 1 second (FEV1) had the main predictive effect but that age, Shwachman score and muPs also had a predictive effect. Identification of mucoid forms of Ps aeruginosa is an unfavorable prognostic factor but the isolation of non-mucoid strains does not appear to be any more important than the isolation of other common respiratory pathogens.     

Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis

By improving pulmonary function in patients with cystic fibrosis (CF), recombinant human deoxyribonuclease (rhDNase) may affect resting energy expenditure (REE). To examine this hypothesis, we measured REE by indirect calorimetry in seven patients with CF before (day 0) and 2 weeks after (day 15) administration of aerosolized rhDNase. Baseline REE was higher in all patients than predicted for age, sex, and weight (mean ± SEM 128±4.9%; range, 116–147%). After 2 weeks of aerosolized rhDNase, mean forced vital capacity (FVC) (in % of predicted values) improved significantly from 54.1 ± 2.2 to 66.3±4.2% (mean improvement, 12.3%; 95% Cl, 2.8,21; P < 0.05) and REE decreased by 11.0% (95% Cl 3.2, 17.5; P < 0.05). In addition, the larger the improvement in FVC in response to rhDNase the greater the decrease in energy expenditure (r – 0.88). The REE decreased in all patients who had an increase in FVC and remained unchanged in two patients who had no change in FVC. We conclude that patients with CF whose lung function improve in response to aerosolized rhDNase have an acute and proportionate reduction in their resting energy expenditure. Pediatr Pulmonol. 1994;18:150–154. © 1994 Wiley-Liss, Inc.     

Respiratory tract colonization with Pseudomonas aeruginosa in cystic fibrosis: correlations between anti-Pseudomonas aeruginosa antibody levels and pulmonary function

Chronic Pseudomonas aeruginosa respiratory tract colonization in patients with cystic fibrosis is associated with development of antibodies to the organism. In contrast to the protection usually afforded by humoral immunity to a bacterial pathogen, the immune response to P. aeruginosa may help perpetuate infection and contribute to pulmonary damage in cystic fibrosis. To determine if specific anti-P. aeruginosa antibody levels correlated with pulmonary dysfunction, we measured antibodies to seven P. aeruginosa serotypes, and correlated the geometric mean titer with pulmonary function tests. Patients were divided into groups without P. aeruginosa colonization (n = 20), with recent colonization (n = 20), and with chronic colonization (n = 60). Noncolonized patients had normal pulmonary function or mild obstructive lung disease, and low anti-P. aeruginosa titers. Pulmonary function tests in recently colonized patients were not different from those of noncolonized patients, but antibody titers were higher. Following colonization FEV1 declined and titers increased rapidly. Patients with chronic colonization had worse pulmonary function and higher titers, but while the former were stable the latter gradually increased. An inverse correlation was found between anti-P. aeruginosa titer and FVC, FEV1, and FEF25-75 (P less than 0.001) in these patients; age was not a factor. The strong correlation between severity of lung disease and anti-P. aeruginosa titer demonstrates that an exaggerated immune response to P. aeruginosa is associated with pulmonary damage in patients with cystic fibrosis.     

Forced expiratory maneuvers in children aged 3 to 5 years

There is no consensus about reproducibility and reliability of spirometry in young children. We evaluated forced expiratory maneuvers from 98 children aged 3 to 5 years with a variety of respiratory disorders before and after bronchodilator treatment. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV,) were analyzed for reproducibility by the American Thoracic Society criteria and for reliability based on the coefficient of variation (CVYo). Over 90% of the patients cooperated, however, while 95% could exhale for at least 1 second, very few generated an FEV, on all 6 “best” efforts. This clearly improved with age. Of all patients nearly 60% performed reproducible pre-and postbronchodilator sets of FVC but only 32% performed reproducible sets of FEV₁. Based on the CV%, those patients who could reproducibly perform an FVC and FEV, did it quite reliably (mean CV%, 9.38 and 7.01 for FVC and FEV₁, respectively). We conclude that while some very young children can perform spirometry, reliability of performance cannot be assumed in this age group. Pediatr Pulmonol. 1994;18:144–149. © 1994 Wiley-Liss, Inc.     

Predictive value of pulmonary function testing during pulmonary exacerbations in cystic fibrosis

The optimal duration of therapy for acute exacerbations of cystic fibrosis (CF) has not been defined, and the utility of serial pulmonary function testing in predicting the duration of therapy has yet to be established. In a review of 90 pulmonary exacerbations of 39 patients with CF requiring hospitalization, we found that 72% of the patients recovered following 2 weeks of intravenous antibiotics and aggressive chest physiotherapy, and that 28% required an extended third week of therapy. Recovery was delayed in patients with more severe chronic pulmonary disease, but the rate of improvement was independent of the degree of pulmonary deterioration with the acute exacerbation. A 40% recovery of FEV, at 1 week was found to correlate significantly with the duration of hospitalization in the 90 patients. When prospectively applied to a second series of consecutively hospitalized patients with CF, 25/28 patients admitted for 2 weeks demonstrated > 40% improvement in FEV, at 1 week, as compared to 5/10 patients subsequently treated for ≤3 weeks (P = 0.030). The predictive values for 2- or 3-week hospitalizations with 1-week interval recovery of > 40% or > 40% in FEV, were 79% and 62%, respectively. These findings suggest that the response to intensive therapy in CF exacerbations is variable and that improvements in pulmonary function after 1 week of therapy may be used to predict the subsequent duration of therapy in the majority of CF patients with pulmonary exacerbations. Pediatr Pulmonol. 1993; 16:227–235. © 1993 Wiley-Liss, Inc.     

Comparison of FEV(3), FEV(6), FEV(1)/FEV(3) and FEV(1)/FEV(6) with usual spirometric indices

Background and objective: Pulmonary function tests play an important role in the management of pulmonary diseases. One of the tests that are widely used is spirometry. Performing an acceptable spirometry manoeuvre according to the standards set by the American Thoracic Society/European Respiratory Society is difficult. The aim of this study was to compare forced expiratory volume in 3 s (FEV₃) and forced expiratory volume in 6 s (FEV₆) with forced vital capacity (FVC), and forced expiratory volume in 1 s FEV₁/FEV₃ and FEV₁/FEV₆ with FEV₁/FVC, in order to substitute the usual spirometric manoeuvres with manoeuvres that are easier to perform. Methods: In a cross‐sectional study, spirometry was performed for 588 subjects who were referred for occupational health evaluations. The accuracy of FEV₃, FEV₆, FEV₁/FEV₃ and FEV₁/FEV₆ was compared with that of FVC and FEV₁/FVC. Chi‐square tests and kappa tests were used to analyse the data. Results: Individuals with normal (n = 297) and abnormal spirometry (n = 291) were evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₁/FEV₆, as compared with that of FEV₁/FVC for detecting obstruction, were 93.56, 99.32, 98.95 and 96.09, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₆, as compared with that of FVC for detecting restriction, were 96.68, 98.65, 96.68 and 98.65, respectively. Conclusions: FEV₆ and FEV₁/FEV₆ can be used as surrogates for FVC and FEV₁/FVC, respectively, and these parameters showed acceptable sensitivity, specificity, positive predictive value and negative predictive value for occupational health evaluations.     

Correlation between specific IgG subclass antibodies to Pseudomonas aeruginosa and opsonic activity in serum from patients with cystic fibrosis

Heat-stable opsonins from sera of patients with cystic fibrosis (CF) non-CF patients with chronic Pseudornonas aeruginosa infection, healthy children, and adults were investigated for their ability to promote phagocytosis of ³⁵S-labeled P. aeruginosa by human polymorphonuclear neutrophils. Healthy children had significantly lower levels of opsonic activity than adults. Sera from patients with CF without chronic P. aeruginosa lung infection showed significantly higher levels of opsonic activity compared to healthy children. Sera from patients with CF in the early stage of chronic infection had similar opsonic activity as non-CF patients with chronic infection. Sera from patients with CF in the late stage of chronic infection had higher opsonic activity than other infected patients, but not different from adult controls. An inverse correlation was found between levels of specific antibodies to P. aeruginosa and opsonic activity in the group of patients in a late stage of infection. An inverse correlation was also found between levels of IgG1 and lgG3 to P. aeruginosa St-Ag and opsonic activity during the late stage of infection. Infection with P. aeruginosa in CF did not induce significantly increased opsonic activity. It seems that antibodies to P. aeruginosa may have inhibitory opsonic activity. Pediatr Pulmonol. 1994; 17:31–40 . © 1994 Wiley-Liss, Inc.     

Ethnic differences in spirometry measurements in China: Results from a large community‐based epidemiological study

Background and objective

No previous studies have examined differences in spirometry measurements among ethnic populations in China, and factors which may influence ethnic differences are unclear. Our study aimed to investigate whether forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) differ among Han Chinese and other ethnic minorities in China.

Methods

We recruited 7137 individuals aged 35–70 years from four areas of China inhabited by ethnic minority groups between 2007 and 2009. We conducted spirometry tests for all available participants, and compared FEV₁ and FVC among Uygur, Hui, Mongolian, Dai and Han Chinese ethnicities, using nonlinear multiplicative regression models.

Results

A total of 2005 healthy never‐smokers were enrolled in the analysis. For all ethnicities, spirometry values increased with height and decreased with age; FEV₁ and FVC were consistently higher in males than in females. Compared with Han Chinese, FEV₁ was 4.42% (95% CI: 2.11–6.78%) higher in Mongolians, 4.08% (95% CI: 1.33–6.76%) lower in Uygurs, 4.39% (95% CI: 1.33–7.35%) lower in Hui people and 4.72% (95% CI: 1.80–7.55%) lower in Dai people, after adjusted for potential confounders including height, age, sex and place of residence. We observed similar differences for FVC.

Conclusions

We detected significant differences in spirometry measurements among ethnic populations in China. Such differences cannot be fully explained by demographic, anthropometric or socioeconomic factors, but may also be attributed to genetic background as well as indoor and outdoor environmental exposures that need further investigation.

     

The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden--the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study

Objectives: To estimate chronic obstructive pulmonary disease (COPD) prevalence in Uppsala and the impact of risk factors on disease prevalence using the standardised methods of the Burden of Obstructive Lung Disease (BOLD) study initiative. Methods: Randomly selected participants, aged 40 years or more (n = 548) responded to a questionnaire regarding smoking habits, respiratory symptoms, medical history, and exposure to airway irritants. Spirometry, with a post‐bronchodilator test, was performed and COPD defined as post‐bronchodilatory forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 0.70 or FEV₁/FVC < lower limit of normality (LLN). Circulatory inflammatory markers were measured. Results: COPD prevalence was 16.2%, which was the fourth lowest prevalence of COPD, compared with 12 other BOLD centres. Main risk factors for COPD were increasing age [odds ratio (OR) = 2.08 per 10 years] and smoking (OR = 1.33 per 10 pack years). Higher education was protective (OR = 0.70 per 5 years). Previous tuberculosis was an almost significant risk factor for COPD (P = 0.08). Subjects with COPD reported more respiratory symptoms but only 29% had previous doctor diagnosed COPD, asthma, chronic bronchitis or emphysema. Participants with COPD had higher levels of C‐reactive protein (P = 0.01), but no difference was observed in interleukin 6 (IL‐6) levels. Using LLN instead of the fixed FEV₁/FVC ratio reduced the prevalence of COPD to 10%. Conclusion: COPD prevalence in Uppsala was similar to other BOLD centres in high‐income countries. Apart from known COPD risk factors (age, smoking, lower educational level), a history of tuberculosis may be associated with COPD even in high‐income countries. COPD remains under‐diagnosed, as only 29% of subjects with COPD had a previously diagnosed lung disorder. Please cite this paper as: Danielsson P, Ólafsdóttir IS, Benediktsdóttir B, Gíslason T and Janson C. The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden – the Burden of Obstructive Lung Disease (BOLD) study: cross‐sectional population‐based study. Clin Respir J 2012; 6: 120–127.     

Serum IgG antibody to outer membrane antigens of Pseudomonas cepacia and Pseudomonas aeruginosa in cystic fibrosis

IgG antibody to the outer membrane of Pseudomonas cepacia was quantified in sera from controls without cystic fibrosis (CF) and from Pseudomonas aeruginosa- and P. cepacia-infected and noninfected patients with CF. The mean antibody titer in the P. cepacia-infected group was significantly higher than that in the other three groups; the mean titer in the P. aeruginosa-infected group was significantly higher than that in the noninfected and control groups. Preabsorption of CF sera with P. cepacia outer membrane produced a significantly lower mean antibody concentration than did matched samples preabsorbed with an equal amount of lipopolysaccharide. By western blot, significantly more P. cepacia-infected patients produced IgG to the 27- than the 36-kilodalton (kDa) porin protein of P. cepacia; 12 of 16 P. aeruginosa-infected patients produced IgG to the 27-kDa porin. Sera from all patients in both groups contained IgG to the porin protein of P. aeruginosa by western blot. We conclude that the 27-kDa porin of P. cepacia is antigenic in most P. cepacia-infected patients with CF and that some P. cepacia outer membrane components may be antigenically related to those of P. aeruginosa.     

Therapeutic methods repeatability of response to hypertonic saline aerosol in children with mild to severe asthma

Non-isotonic aerosols are being used more commonly to perform bronchial provocation tests. In contrast to histamine and methacholine challenge tests they appear to have higher specificity and a higher predictive value. The aim of the present study was to assess the reproducibility of the response to challenge with 4.5% hypertonic saline administered via an ultrasonic nebulizer in children with mild to severe asthma. Seventeen children with asthma aged 10 to 14 years completed two or three challenge tests at the same time of day within a 10 day period. Of these 17 children 9 had mild, 4 moderate, and 4 severe asthma. Children inhaled 4.5% hypertonic NaCl from an ultrasonic nebulizer with an output of 1.9 to 2.5 mL/min (Timeter) using the protocol developed by Anderson with modifications. A fall in forced expiratory volume in 1 second (FEV₁) from baseline of 15% or more was considered a positive response and PD₁₅, was calculated. In 16/17 subjects a greater than 15% fall in FEV₁ occurred consistently on all study days. One subject with moderate asthma had a less than 15% fall in FEV₁ on both study days. The coefficient of repeatability for PD₁₅ was 1.8. This equals 0.85 of a doubling dose difference between the two or three measurements of PD₁₅. The cumulative time of aerosol inhalation causing a fall in FEV₁ 2 15%) (PT₁₅) showed a coefficient of repeatability of 1.59, similar to 0.67 doubling dose difference. The PD₁₅ and PT₁₅ were highly significantly correlated. The 4.5% NaCl challenge test yields good reproducibility in children with mild to severe asthma under laboratory conditions. Pediatr Pulmonol. 1994;18:330–336 © Wiley-Liss, Inc.