Response to bronchodilator and clinical, pathophysiological features in patients with nonasthmatic eosinophilic bronchitis.

INTRODUCTION: Whether nonasthmatic eosinophilic bronchitis (NAEB) shows response to bronchodilator (RB) remains unclear. OBJECTIVES: To investigate the RB and its relationship with clinical and pathophysiological features in NAEB. METHODS: Fifty-one patients with NAEB were assigned in a 2:1 ratio to receive oral bambuterol hydrochloride (n = 34, 10 mg, once daily, for 3 days) or matched placebo (n = 17) randomly, of whom 48 patients (32 with bronchodilator and 16 with placebo) completed the study. Sputum induction, spirometry and cough reflex sensitivity were measured. RB was considered when cough Visual analogue scale (VAS) score decreased 30% or more after treatment. Cough reflex sensitivity was defined as the lowest concentration of capsaicin inducing five coughings or more (C5), and presented as Log C5. RESULTS: The responsive rate of patients with bronchodilator was significantly higher than that with placebo (34.4% vs 6.3%, P < 0.05). The VAS score decreased significantly in patients with bronchodilator (median: 6.0-3.0, P < 0.01). There was a significantly higher median Log C5 (2.7 vs 1.3, P < 0.05), and a higher trend of decline in FEV1 % predicted and MMEF% predicted after bronchial provocation in patients with RB as compared with patients without RB. No significant differences in baseline percentages of sputum eosinophil were found between patients with RB and that without RB. CONCLUSIONS: One third of patients with NAEB respond well to bronchodilator treatment, which are related with lower cough reflex sensitivity and increased airway responsiveness. The relationship between NAEB and asthma needs to be investigated further.

Systemic inflammation and the effects of short-term antibiotic treatment for PPM positive patients with stable COPD.

Objective: To evaluate patients with stable COPD for the presence of potentially pathogenic microorganisms (PPM), systemic inflammation and the effects of short-term antibiotic therapy in PPM positive patients. Methods: From January 2016 to June 2017, we enrolled 96 stable COPD patients. Bacterial cultures from sputum collections were quantitated, along with markers for systemic inflammation including serum C-reactive protein (CRP), interleukin-8 (IL-8) and plasma fibrinogen (FIB) in all patients. All enrolled patients were followed for 12 months. Forty patients were identified as PPM positive and were randomly divided into an antibiotic group and a control group. The antibiotic group was treated with moxifloxacin orally for 6 days. Lung function and markers for systemic inflammation were repeatedly measured at 30 days and 6 months in PPM positive subjects. Results: Binary logistic regression analysis showed that risk factors for PPM positive are bronchiectasis (OR 4.18, 95% CI 1.20-14.59; P=0.025), COPD assessment test (CAT) ≥20 (OR 17.55, 95% CI 2.82-109.18; P=0.002), spontaneous sputum (OR 15.09, 95% CI 1.36-168.02; P=0.027) and sputum purulence (OR 38.43, 95% CI 5.39-274.21; P=0.000). CRP and IL-8 were higher in PPM positive group than those in PPM negative group (P=0.001, P=0.007, respectively), but there were no differences of FIB between the two groups (P=0.086). Compared to the PPM negative group, the rate of acute exacerbation of COPD was higher (P=0.029) and time to next acute exacerbation was shorter (P=0.030) in PPM positive group. There were no differences in lung function and systemic inflammatory markers either in the control group or the antibiotic group at different time points of follow-up. Conclusion: PPM exists in stable COPD patients and can cause systemic inflammation and is associated with acute exacerbation of COPD. Short-term antibiotic therapy had no effect on systemic inflammation nor on acute exacerbation of COPD.China Clinical Trials Registry: ChiCTR-IOR-15006769.

Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression.

BACKGROUND: Vitamin D is a molecule that modulates the immune response and shows anti-inflammatory effects that are beneficial for the control of chronic diseases such as asthma. The trial aim was to explore the effect of vitamin D supplementation on the colonization of pathogenic bacteria in the upper respiratory tract of allergic asthmatic patients. METHODS: This study was conducted in 86 patients between 18 and 50 years of age who were randomly divided into two groups. Both groups received the treatment recommended by the Global Initiative for Asthma (GINA). One group also received calcitriol (1,25-(OH)2D3), and the other group received a placebo. At baseline and 6 months, skin prick tests were conducted, pharyngeal bacterial cultures were performed, and cathelicidin LL-37 was measured in sputum. Serum levels of IgE, eosinophils, IL-5, IL-9, IL-10, IL-13, and IFNγ were quantified at the beginning and the end of the study. RESULTS: Serum levels of IL-10 and IFNγ increased significantly in the group of patients with vitamin D supplementation, while IL-5, IL-9, and IL-13 decreased significantly. At the end of the trial, IgE and eosinophil levels significantly decreased but allergen sensitivity did not show any changes from baseline. Respiratory infections were drastically reduced, and this decrease was related to the number of patients who had high serum levels of IL-10 and IFNγ and expressed LL-37 in their sputum. CONCLUSION: Treatment of asthma patients with vitamin D reduced respiratory infections, and this effect was related to the increase of cathelicidin LL-37.

High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.

BACKGROUND: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. OBJECTIVE: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. DESIGN: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. RESULTS: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). CONCLUSION: A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086.

Novel biomarkers for asthma stratification and personalized therapy.

A stepwise pharmacological treatment is currently recommended for all asthma patients and is personalized mainly on disease severity, aiming for the lowest disease-controlling step. Nevertheless, asthma comprises several related pathologies with similar clinical manifestations resulting from distinct underlying mechanisms. Therefore novel biomarkers could lead to asthma stratification and thus improve upon the current stepwise approach. The aim of this review is to update the reader with regard to different assays proposed in the recent asthma literature for measuring potential biomarkers for patient stratification and treatment personalization. Promising biomarkers are sputum eosinophils, serum periostin and exhaled nitric oxide. Periostin could differentiate between Th2-high and Th2-low asthma (Th2-high patients are more responsive to glucocorticoids) and the less-defined asthma types which often present a therapeutic challenge. Several other biomarkers, mainly cytokines, leukotrienes and exhaled air components, can be quantified in body fluids and exhaled breath and could also be useful for asthma stratification.

Bronchial inflammation in seasonal allergic rhinitis with or without asthma in relation to natural exposure to pollen allergens.

BACKGROUND: Nasal inflammation in allergic rhinitis enhances bronchial Th2 driven inflammation and development of asthma. We assessed bronchial inflammation induced by natural allergen exposure during pollen season in patients with pollinosis with or without asthma to show the intensity of inflammation in asthma and rhinitis and possible persistence of inflammation in periods without allergen exposure. METHODS: Sputum was induced in 52 patients with seasonal allergic rhinitis without asthma, 38 patients with seasonal allergic rhinitis and seasonal asthma and 23 healthy volunteers. Sampling was performed 6-8 weeks before the expected beginning of symptoms, during symptomatic period and 6-8 weeks after the end of symptoms. Sputum ECP was measured by means of chemi-luminiscent immunometric assay and sputum cell counts were assessed by classical staining and immunocytochemistry. RESULTS: Sputum eosinophils were on the whole higher in both asthma and rhinitis compared to controls (p<0.001, p=0.003). The rise of eosinophils during pollen season compared with values out of pollen season was significant in asthma (classical staining) (p=0.014) and slightly apparent in rhinitis (immunocytochemistry) (p=0.073). The seasonal rise of sputum ECP was observed only in rhinitis (p=0.006). CONCLUSIONS: Inflammation of the lower airway in patients with allergic rhinitis with and without asthma has been confirmed by means of both sputum eosinophil count and sputum ECP level. Persistent inflammation of lower airway in periods without allergen exposure was proven in seasonal asthma. This may have implications for the therapy of seasonal allergic rhinitis with and without asthma in terms of promoting long-term anti-inflammatory treatment.

Effects of ex vivo γ-tocopherol on airway macrophage function in healthy and mild allergic asthmatics.

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate γ-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6) and mild house dust mite-sensitive allergic asthmatics (n = 6) were treated ex vivo with GT (300 µM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused downregulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor.

Eotaxin, but not IL-8, is increased in upper and lower airways of allergic rhinitis subjects after nasal allergen challenge.

The aim of this study was to assess the impact of a single nasal allergen challenge (NAC) on levels of eotaxin and IL-8 and the inflammatory cells in upper and lower airways of allergic rhinitis (AR) patients. Twenty-four AR patients and 12 control subjects entered a sequential nasal placebo challenge and NAC study, out of the pollen season. Nasal lavage fluid (NLF) was obtained at baseline, 15 minutes, and 1, 5, and 24 hours postchallenge. Before and 24 hours after placebo/allergen challenge induced sputum was performed. NLF and induced sputum were evaluated for total cell count (TCC) and differential cell count and analyzed for concentrations of eotaxin and IL-8 using ELISA method. NAC in AR subjects was associated with significantly increased sputum (p = 0.008) and NLF (p < 0.001) eotaxin levels. Post-NAC IL-8 levels were significantly increased in NLF (p < 00001) but not in sputum (p = 0.080) of AR subjects. Increased eotaxin levels in NLF positively correlated with the increased TCC and eosinophils. Positive correlations were also found between NLF increased eotaxin level and sputum TCC, eosinophils, and macrophages. NAC is associated with the increased levels of eotaxin in lower airways of AR subjects. Allergen-induced secretion of eotaxin in nasal mucosa of AR subjects is involved in determining the cellular character of both upper and lower airway inflammation.

Probiotic supplementation affects pulmonary exacerbations in patients with cystic fibrosis: a pilot study.

OBJECTIVE: Probiotics reduce intestinal inflammation in, and Lactobacillus GG (LGG) reduces pulmonary exacerbation rate cystic fibrosis (CF) patients. We intended to determine the effect of a mixed probiotic preparation on pulmonary exacerbations and inflammatory characteristics of the sputum in CF patients. STUDY DESIGN: A prospective pilot study of 10 CF patients with mild-moderate lung disease and Pseudomonas aeruginosa colonization, treated with probiotics for 6 months. Pulmonary function tests (PFT's), sputum cultures with semi-quantitative bacterial analysis, and sputum neutrophil count and interleukin-8 (IL-8) levels were compared to pre-treatment and post-treatment values. The rate of pulmonary exacerbations was compared to 2 years prior to the study. RESULTS: The exacerbation rate was significantly reduced in comparison to the previous 2 years and to 6 months post-treatment (P = 0.002). PFT's have not changed at the end of treatment and during 6 months post-treatment. No change in sputum bacteria, neutrophil count, and IL-8 levels was observed. CONCLUSION: Probiotics reduce pulmonary exacerbations rate in patients with CF. Probiotics may have a preventive potential for pulmonary deterioration in CF patients.

Fluticasone propionate protects against ozone-induced airway inflammation and modified immune cell activation markers in healthy volunteers.

BACKGROUND: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O(3)-induced airway inflammation, but their effect on innate immune activation is unknown. OBJECTIVES: We used a human O(3) inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers. METHODS: Seventeen O(3)-responsive subjects [>10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O(3) challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O(3) challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation. RESULTS: FP had no effect on O(3)-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O(3)-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O(3)-induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner. CONCLUSIONS: This study confirmed and extended data demonstrating the protective effect of FP against O(3)-induced airway inflammation and immune cell activation.

A pilot study on the safety and efficacy of a novel antioxidant rich formulation in patients with cystic fibrosis.

BACKGROUND: Pancreatic insufficiency and a diminished bile acid pool cause malabsorption of important essential nutrients and other dietary components in cystic fibrosis (CF). Of particular significance is the malabsorption of fat-soluble antioxidants such as carotenoids, tocopherols and coenzyme Q(10) (CoQ(10)). Despite supplementation, CF patients are often deficient in these compounds, resulting in increased oxidative stress, which may contribute to adverse health effects. This pilot study was designed to evaluate the safety of a novel micellar formulation (CF-1) of fat-soluble nutrients and antioxidants and to determine its efficacy in improving plasma levels of these compounds and reducing inflammatory markers in induced sputum. METHODS: Ten CF subjects, ages 8 to 45 years old, were given orally 10 ml of the CF-1 formulation daily for 56 days after a 21-day washout period in which subjects stopped supplemental vitamin use except for a standard multivitamin. Plasma obtained at -3, 0 (baseline), 1, 2, 4, and 8 weeks was assayed for beta-carotene, gamma-tocopherol, retinol, and CoQ(10) as well as for safety parameters (comprehensive metabolic panel and complete blood count). In addition, pulmonary function was measured and induced sputum was assayed for markers of inflammation and quantitative bacterial counts both prior and during dosing. RESULTS: No serious adverse effects, laboratory abnormalities or elevated nutrient levels (above normal) were identified as related to CF-1. Supplementation with CF-1 significantly increased beta-carotene levels at all dosing time points when compared to screening and baseline. In addition, gamma-tocopherol and CoQ(10) significantly increased from baseline in all subjects. Induced sputum myeloperoxidase significantly decreased and there was a trend toward decreases in PMN elastase and total cell counts with CF-1. There was a significant inverse correlation between the antioxidant levels and induced sputum changes in IL-8 and total neutrophils. Lung function and sputum bacterial counts were unchanged. CONCLUSION: The novel CF-1 formulation safely and effectively increased plasma levels of important fat-soluble nutrients and antioxidants. In addition, improvements in antioxidant plasma levels were associated with reductions in airway inflammation in CF patients.

Safety and application of induced sputum analysis in childhood asthma.

BACKGROUND: The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess airway inflammation in children, because bronchoscopy and biopsy carry some risk. The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers. OBJECTIVE: At the Denver CAMP site, we sought to evaluate the safety of sputum induction, to determine differences in airway inflammation between treatment groups by using induced sputum analysis, and to examine correlations between other biomarkers and sputum eosinophils. METHODS: Sputum induction was performed, and exhaled nitric oxide, circulating eosinophil counts, and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout. Spirometry and a methacholine challenge were also performed according to the CAMP protocol. RESULTS: Ninety of 117 children provided an adequate sputum sample for analysis. In 9 subjects (3 nedocromil and 6 placebo), sputum induction resulted in bronchospasm. These subjects had greater disease severity, as measured by a lower median prebronchodilator FEV 1 percentage predicted (85.0% vs 96.0%; P =.024) and FEV 1 /FVC ratio (70.0% vs 79.0%; P =.0008); greater bronchodilator reversibility (16.5% vs 6.8%; P =.004); higher serum IgE (1390.0 vs 495.0 ng/mL; P =.017) and circulating eosinophil count (757.0 vs 282.0/mm 3; P =.04); greater use of prednisone (1.9 vs 0.9 courses per 100 person-years; P =.05); and greater supplemental inhaled steroid doses (85.3 vs 0 mg; P =.016). At treatment discontinuation, budesonide-treated patients had a lower median (1st, 3rd quartile) sputum percentage eosinophil (SPEos) (0.2% [0%, 1.2%] vs 0.8% [0.2%, 4.6%]; P =.03) compared with those treated with placebo; no significant difference was noted between nedocromil- and placebo-treated patients. Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone (n = 23) during the washout period compared with patients who remained stable (3.6% [0.4%, 6.4%] vs 0.6% [0.2%, 3.2%] SPEos; P =.023). Finally, greater SPEos was associated with atopy, higher bronchodilator reversibility, lower FEV 1 /FVC ratio, higher exhaled nitric oxide levels, circulating eosinophils, sputum and serum eosinophil cationic protein, more prednisone courses during the treatment period, and greater asthma severity. CONCLUSIONS: Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control. However, this procedure still remains a research tool in asthma because of its requirements for technical expertise.

A randomized, controlled study of specific immunotherapy in monosensitized subjects with seasonal rhinitis: effect on bronchial hyperresponsiveness, sputum inflammatory markers and development of asthma symptoms.

Allergic rhinitis is often associated with bronchial hyperresponsiveness (BHR) and airway inflammation, and it seems to be an important risk factor for the development of asthma. Specific immunotherapy (SIT) reduces symptoms and medication requirements in subjects with allergic rhinitis, but the mechanisms by which SIT promotes these beneficial effects are less clear. We have investigated the effects of Parietaria-SIT on rhinitis symptoms, BHR to inhaled methacholine, eosinophilic inflammation and cytokine production (interferon gamma and interleukin-4) in the sputum. The effect on asthma progression was also examined. Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to Parietaria judaica participated in a randomized, double-blind, placebo-controlled, parallel group study. Participants were randomly assigned to receive injections of a Parietaria pollen vaccine (n = 15) or matched placebo injections (n = 15) in a rapid updosing cluster regimen for 7 weeks, followed by monthly injections for 34 months. Throughout the 3-year study we collected data on symptoms and medication score, airway responsiveness to methacholine, eosinophilia and soluble cytokines in sputum, followed by a complete evaluation of the clinical course of atopy. Hay fever symptom and medication scores were well controlled by SIT. By the end of the study, in the placebo group, symptom and medication scores significantly increased by a median (interquartile range) of 121% (15-280%) and 263% (0-4400%) respectively (p < 0.01), whereas no significant difference was observed in the SIT group. We found no significant changes in the sputum parameters and methacholine PC15 values in both groups throughout the study. By the end of the investigation, a total of 9 out of 29 participants developed asthma symptoms; of these, seven (47%) belonged to the placebo group, whereas only 2 (14%) to the SIT-treated group (p = 0.056). In conclusion, Parietaria-SIT is effective in controlling hay fever symptoms and rescue medications, but no changes in the BHR to methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma, suggesting that SIT should be considered earlier in the management of this condition.

Eosinophil apoptosis in induced sputum from patients with seasonal allergic rhinitis and with asymptomatic and symptomatic asthma.

BACKGROUND: Eosinophilic inflammation is known to play an important role in the pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is characterized by morphologic cell changes and leads to recognition and ingestion by macrophages. Apoptosis could be an important mechanism controlling the resolution of tissue eosinophilia. OBJECTIVE: This study was designed to investigate the presence of apoptotic eosinophils in induced sputum of patients with seasonal allergic rhinitis (SAR), when examined during natural pollen exposure and of patients with perennial asthma of different degrees of severity. METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The severity of asthma was assessed by clinical scoring. Sputum was induced following a standard method and differential cell count was estimated. Eosinophils showing cell shrinkage and nuclear coalescence were classified as apoptotic. The number of apoptotic eosinophils was expressed as the percentage of total cells in sputum and as the proportion of apoptotic eosinophils relative to normal bilobed eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in the SA group was significantly greater than that in the SAR and the AA groups (P < .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA group was significantly lower than that in the SAR group (P < .001) and in the SA group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was significantly greater than in the AA group (P < .05) and in the SA group (P < .05). There was no difference in the apoptotic ratio between the AA and SA groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are detectable in induced sputum of allergic patients. Further, the results of our study suggest that apoptosis could be an important mechanism in the control of acute eosinophilic inflammation in patients with SAR exposed to the sensitizing antigens. It appears that the apoptotic mechanism could be less effective in controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic inflammation.

Analysis of induced sputum for studying allergen-specific IgE antibodies in airway secretion from asthmatic patients.

BACKGROUND: Allergen-specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma. However, studies on allergen-specific IgE antibodies in airway secretion from asthmatic patients are very rare compared with those in serum. OBJECTIVES: The present study was undertaken to determine whether induced sputum might provide a useful method for analysing allergen-specific IgE antibodies in airway secretions from asthmatic patients. METHODS: Specific IgE antibodies to house dust mite (HDM) antigen were measured in induced sputum from 10 HDM-sensitive asthmatic patients and 12 non-allergic controls by enzyme-linked immunosorbent assay. HDM-specific IgE was regarded as positive when the absorbance value was higher than mean + 2SD of controls. Their antigen-binding characteristics were determined by immunoblot analysis. RESULTS: HDM-specific IgE was positive in induced sputum from seven of 10 HDM-sensitive asthmatics. The IgE binding to HDM antigen could be inhibited by fluid phase HDM antigen in a dose-dependent manner, not by mugwort antigen. Treatment of induced sputum with dithiothreitol decreased the antigen-specific bindings, and increased the non-specific bindings on the measurement of HDM-specific IgE. These effects were significant in a concentration of dithiothreitol greater than 0.05%. Immunoblot analysis revealed that HDM-specific IgE antibodies in induced sputum recognized the HDM antigens with molecular weights of 42, 34, 32, 25 and 14 kDa. These antigen binding characteristics were similar to those in serum. CONCLUSION: We conclude that analysis of induced sputum is a useful non-invasive method for studying allergen-specific IgE antibodies in airway secretion from asthmatic patients.

[The use of an aerosol of natural brine and of sinusoidal modulated currents in chronic pneumonias in children]. / Primenenie aérozolia rapy i sinusoidal'nykh modulirovannykh tokov pri khronicheskikh pnevmoniiakh u detei.

Inhalations of 1% natural brine in combination with SMC electrophoresis of 1% natural brine above the lesion proved to ensure good correction of the defense of respiratory tract mucosa and to prolong remission to 15-18 months. This method can be applied in sanatoria, in rehabilitation centers, in pulmonary disease departments.

Alpha 1-proteinase inhibitor abrogates proteolytic and secretagogue activity of cystic fibrosis sputum.

Airway disease in cystic fibrosis (CF) is characterized by neutrophil-dominated chronic inflammation with an excess of uninhibited neutrophil elastase (NE), which is regarded as an important factor in progressive lung destruction. Therefore, inhalation of alpha 1-proteinase inhibitor (alpha 1-PI) seems to be a reasonable therapeutic approach. To estimate its therapeutic potential, we quantitatively investigated the in vitro interactions of exogenous alpha 1-PI with CF sputum samples (n = 28). High NE and alpha 1-PI concentrations were detected in CF sputum (6.03 +/- 0.78 and 2.56 +/- 0.16 mumol/l, respectively). There was significant NE activity (2.6 +/- 0.4 U/l) due to both the surplus of NE and proteolytic degradation of alpha 1-PI. Addition of exogenous alpha 1-PI resulted in a dose-dependent inhibition of NE activity in CF sputum; > 90% inhibition was achieved at 10 micrograms/ml alpha 1-PI. Purified NE as well as CF sputum potently induced secretion from porcine tracheal glands. Corresponding to inhibition of NE activity, CF sputum-induced secretion was also inhibited by exogenous alpha 1-PI; > 90% inhibition was also achieved at 10 micrograms/ml alpha 1-PI. Incubation of exogenous alpha 1-PI with CF sputum for 24 h did not reduce the inhibitory effects. From our in vitro results we conclude that inhalation of alpha 1-PI might effectively inhibit both NE activity and airway gland hypersecretion in CF airways.

[The efficacy of the natural antibacterial preparation chlorophyllypt in the combined treatment of acute lung abscesses]. / Effektivnost' prirodnogo antibakterial'nogo preparata khlorofillipta v kompleksnoi terapii ostrykh abstsessov legkikh.

The complexity of the treatment of acute suppurative pulmonary diseases has been aggravated recently by the growth of microbial resistance to antibiotics and enhancement of the allergy incidence among the population. This circumstance restricts the use of antibiotic on a broad scale in clinical practice and makes the researchers go in studies of adequate substitutes. In the given case, use was made of chlorophyllipt. It was given to patients by intravenous drip in the form of a 0.25% solution based on saline twice a day. To increase local deposition of the administered antimicrobial drug in the affected area, interstitial electrophoresis was employed. In the patients' group on chlorophyllipt, the clinico-laboratory and x-ray parameters returned to normal earlier. Chlorophyllipt was noted to produce an immunocorrective action characterized by the normalization of the absolute count and percentage of E-RFC and theophylline-resistant-RFC. This action could not be observed in the patients' group receiving only antibiotics.

Treating community-acquired lower respiratory infection.

Despite the proliferation of antibiotics, pneumonia remains a leading cause of death in the United States. Diagnostic methods for identifying pathogenic organisms in pneumonia frequently are inaccurate or unreliable, and may be unproductive. When the precise etiology has not been determined, a second-generation cephalosporin offers wide antibiotic coverage as initial therapy for patients with community-acquired bacterial pneumonia.

Quantitation of proteins in sputum from patients with chronic obstructive lung disease. I. Determination of immunoglobulin A.

Samples of sputum from nine patients with chronic obstructive lung disease were collected every morning for 5 consecutive days, and their mean apparent viscosities were determined. After a standard solubilization procedure, the concentration of immunoglobulin A (IgA) in each sample was determined by quantitative immunodiffusion and also by an immunofluorimetric method, using dimeric IgA purified from colostrum as a standard. The two methods gave diverging results probably reflecting different sensitivities of the techniques to various classes of IgA (monomers, dimers and polymers). The concentration of IgA was found to vary from 1.2 to 3.9 g/l with a mean value of 2.3 g/l for the 45 samples using the immunodiffusion technique, and from 1.3 to 4.9 g/l with a mean value of 3.5 g/l using the immunofluorimetric method. In agreement with earlier observations, a weak correlation was shown between the concentration of IgA in the samples and their mean viscosities. A similar correlation was, however, demonstrated between IgA and the total content of protein in the soluble part of the samples. It could therefore not be decided whether IgA itself or other proteins in the sputa were responsible for the observed effect on viscosity.