Lower Respiratory Tract Inflammation Research Articles

Molecular typing of Mycoplasma pneumoniae and its correlation with macrolide resistance in children in Henan of China

Background/purposeAs a major causative pathogen of community-acquired pneumonia, Mycoplasma pneumoniae (M. pneumoniae) can cause both upper and lower respiratory tract inflammation as well as extrapulmonary syndromes, especially in infants and the elderly. The emergence of macrolide–resistance has significant effects on the treatment of relevant diseases in children. This study aimed to analyze the genotypes and the macrolide resistance-associated mutations in M. pneumoniae sampled from the pediatric patients in Henan, China. MethodsA segment of gene on the 23S rRNA was amplified and sequenced to detect the mutations related to macrolide resistance. Molecular typing was performed by the method named multiple locus variable-number tandem repeat analysis (MLVA) for macrolide-susceptible and macrolide-resistant specimens. ResultsAmong the M. pneumoniae-positive samples, 95.7% (111/116) had macrolide-resistant mutation, and all of them consisted of the A2063G mutation. There were only two MLVA types identified in this study, type 4-5-7-2 (51/92, 55.4%) and type 3-5-6-2 (41/92, 44.6%). ConclusionThere was no correlation between MLVA types and macrolide resistance (P ​> ​0.05).

Оптимальное лечение инфекционного риносинусита как инструмент профилактики обострений ХОБЛ

Background: many studies report on the association between upper and lower respiratory infections. Various theories explain this association. In particular, some evidence demonstrates that nasal symptoms in diseases of the nasal cavity and paranasal sinuses affect exacerbations of chronic obstructive pulmonary disease (COPD). Therefore, treatment for rhinosinusitis improves the overall health and quality of life of these patients. Aim: to assess the clinical efficacy, tolerability, and safety of a combined antibacterial, anti-inflammatory, and vasoconstrictive drug in mild and moderate acute rhinosinusitis and concomitant COPD. Patients and Methods: this study enrolled 50 male and female patients aged 41–65 years. The primary examination included complaints and history taking, examination, instrumental tests for ENT organs, and pulmonary consultation. All patients underwent digital diaphanoscopy during the first visit to rule out acute exudative rhinosinusitis. In addition, all patients filled out a subjective assessment questionnaire. Treatment continued for 10 days with an interim examination on day 5±1 after starting treatment. Study group patients received a combined drug Polydexa with phenylephrine (1 injection into each nostril 4 times daily for 10 days) and irrigation with isotonic saline. The control group patients received 2 doses of mometasone furoate twice daily into each nostril for 10 days and irrigation with isotonic saline. Topical vasoconstrictors were allowed to be used as needed. Results: significant differences in the improvement of inflammatory symptoms between the groups were reported as early as by the second visit. The effect occurred earlier and was more significant at all treatment steps in the study group. A natural association between upper respiratory infection (acute rhinosinusitis), treatment strategy choice, and COPD exacerbation was revealed. Meanwhile, more COPD exacerbations were detected in the control group than in the study group (7 vs. 4). Conclusion: in mild and moderate acute rhinosinusitis and concomitant COPD, the combined drug Polydexa with phenylephrine reduces the rate and severity of COPD exacerbations. KEYWORDS: rhinosinusitis, nasal symptoms, upper and lower respiratory tract inflammation, Haemophilus influenzae, chronic obstructive pulmonary disease, phenylephrine, neomycin sulfate, polymixin B. FOR CITATION: Ovchinnikov A.Yu., Miroshnichenko N.A., Nikolaeva Yu.O., Zaitsev A.A. Optimal treatment for infectious rhinosinusitis as a tool to prevent COPD exacerbations. Russian Medical Inquiry. 2023;7(8):511–517 (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-6.

Mycoplasma pneumoniae Infections: Pathogenesis and Vaccine Development.

Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. Refractory pneumonia caused by M. pneumonia can be life-threatening, especially in infants and the elderly. Here, based on a comprehensive review of the scientific literature related to the respective area, we summarize the virulence factors of M. pneumoniae and the major pathogenic mechanisms mediated by the pathogen: adhesion to host cells, direct cytotoxicity against host cells, inflammatory response-induced immune injury, and immune evasion. The increasing rate of macrolide-resistant strains and the harmful side effects of other sensitive antibiotics (e.g., respiratory quinolones and tetracyclines) in young children make it difficult to treat, and increase the health risk or re-infections. Hence, there is an urgent need for development of an effective vaccine to prevent M. pneumoniae infections in children. Various types of M. pneumoniae vaccines have been reported, including whole-cell vaccines (inactivated and live-attenuated vaccines), subunit vaccines (involving M. pneumoniae protein P1, protein P30, protein P116 and CARDS toxin) and DNA vaccines. This narrative review summarizes the key pathogenic mechanisms underlying M. pneumoniae infection and highlights the relevant vaccines that have been developed and their reported effectiveness.

Enzymatic Markers of Pulmonary Inflammation in Tracheal Wash Fluid in Racehorses: Alkaline Phosphatase and Lactate Dehydrogenase

Background: Diagnosis of the lower airway diseases (LAD) in horses relies on clinical signs, endoscopic examination and cytologic evaluation of lower respiratory tract flushing fluids as well. Specific enzyme activities in respiratory tract fluids of horses could be used as useful indicators in lower airway disorders. The main goal of the study was to evaluate the diagnostic usefulness of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzyme activites in tracheal wash (TW) fluids of horses with lower respiratory tract inflammation and/or damage and also in distinguishing of non-septic and septic inflammation in racehorses with LAD.Materials, Methods & Results: A cross-sectional study was conducted in racehorses. TW fluid samples were obtained from 83 racehorses (71 with lower airway diseases and 12 healthy controls) for the study. The One-Way ANOVA Test was used for the significance analysis of the differences between the groups in showing the normal distribution of blood serum ALP and LDH properties. Kruskal Wallis H Test and Tamhane T2 test were used for the significance analysis of the differences between the groups of tracheal ALP and LDH properties, which were not normally distributed. The sampled horses were classified into 3 groups as healthy control, non septic neutrophilic inflammation (NS-LAD) and septic neutrophilic inflammation (S-LAD) according to the tracheal mucus scores determined during endoscopic examination, clinical signs, cytologic and bacteriologic examination of collected TW samples. According to cytology results normal neutrophil levels (< 20%) were determined in the heatlhy control group (14.5%). However, increased neutrophil levels (≥ 20% and ≥ 80%) were encountered in the NS-LAD (61.4%) and S-LAD (24.1%) groups respectively. Also, the signs of degenerative changes and presence of intracellular bacteria in the neutrophil cells in the S-LAD group was observed. Bacteriologic analysis of the samples revealed Streptococcus equi subsp. zooepidemicus was the most prevalent agent (85.6%) followed by Escherichia coli (4.8%), Staphylococcus aureus (4.8%) and Klebsiella pneumoniae (4.8%). ALP and LDH enzyme activities of TW fluid were found to be significantly higher in racehorses with LAD compared with healthy controls (P < 0.01). On the other hand, a significant difference was also determined for LDH levels between NS-LAD and S-LAD cases determining with cytological and bacteriological examination (P < 0.01). No statistically significant difference was found between NS-LAD and S-LAD group. Serum ALP and LDH levels of racehorses revealed no significant difference between each study groups.Discussion: Respiratory system diseases have been known to be one of the main causes of training disruption and interruption of racing events in racehorses. Specifically, LAD is the most frequently diagnosed disorder in racehorses evaluated for poor performance. In the present study established for determining the usefulness of ALP and LDH enzyme levels in the TW samples of horses with lower respiratory tract inflammatory disorders. It was concluded that ALP and LDH enzyme activities of TW fluid could be considered as indicators of pulmonary inflammation and/or damage and LDH enzyme activity is thought to be useful in distinguishing neutrophilic non-septic and septic pulmonary inflammation in racehorses with LAD. On the other hand, data obtained from the study indicated that TW fluid ALP activity was not enough statistically to differenatiate horses with non-septic and septic lower airway inflammation.

The next-generation combination drugs as part of the comprehensive therapy for inflammatory diseases of the pharynx

Inflammatory diseases of the pharynx constitute one of the most significant nosologies groups in the ENT organ diseases profile. According to modern epidemiological data, acute and chronic tonsillopharyngitis are inferior only to influenza and other forms of ARVI with predominantly nasal and paranasal sinuses, as well as the lower respiratory tract inflammation in prevalence among the population. Infectious pathogens are the most common etiology of inflammatory diseases of the pharynx. Accordingly, the pharmacological agents should be selected among the drugs having pronounced antimicrobial activity against both bacterial and other organisms - viral and fungal, and an analgesic effect, as sore throat is the main symptom of tonsillofingitis. The combination preparation Septolete® total is one of such drugs.

Single nucleotide polymorphisms of TLR-2, TLR-3, TLR-4 and susceptibility to inflammatory diseases of the respiratory tract

The aim of the research is to establish an association between Arg753Gln polymorphism of TLR-2 gene, Leu412Phe of TLR-3 gene, Asp299Gly of TLR-4 gene and susceptibility to inflammatory diseases of the upper and lower respiratory tract and the complicated forms of АRI development. Materials and methods . 98 healthy subjects distributed according to the genotype of TLR-2, TLR-3, TLR-4 were enrolled in the study of association between Arg753Gln polymorphism of TLR-2, Leu412Phe of TLR-3 and Asp299Gly of TLR-4 genes and inflammatory diseases of the upper and lower respiratory tract. The polymorphic site of TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly genotyping was performed by polymerase chain reaction using oligonucleotide primers. The relative risk of the disease and complications development was estimated using the odds ratio with 95 % confidence interval. The statistical significance of differences in qualitative characteristics was evaluated using Fischer's exact test. Results. It has been revealed that individuals with polymorphic TLR-2, TLR-3 and TLR-4 genes have an increased susceptibility to АRI with frequent episodes during the year that are complicated by lower respiratory tract inflammation as well as chronic inflammatory diseases of the upper respiratory tract. It has been shown that the risk of bronchitis and pneumonia development in АRIs is higher in subjects with polymorphic genotypes of TLR-2, TLR-3 and TLR-4 as compared to the carriers of normal alleles distribution: 2.9 times with Leu/Phe genotype of TLR-3, 20.0 times with Phe/Phe of TLR-3 and 12.8 times with combinations of polymorphic genotypes of TLR-2, TLR-3, TLR-4. Conclusions. The results of the study indicate that the presence of single-nucleotide polymorphisms TLR-2 Arg753Gln, TLR-3 Leu412Phe and TLR-4 Asp299Gly is the marker of high susceptibility to respiratory diseases. Individuals with polymorphic status of TLR-2, TLR-3 and TLR-4 genotypes have an increased susceptibility to inflammatory diseases of the upper and lower respiratory tract with АRI frequency of 4 or more episodes during the year.

Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans.

IntroductionNaturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The “experimental cold model” is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity.Methods40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis.ResultsInfection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10.ConclusionUpon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.

Allergic Rhinitis and Chronic Upper & Lower Respiratory Tract Inflammation

Allergic Rhinitis and Chronic Upper & Lower Respiratory Tract Inflammation

Radon-enriched hot spring water therapy for upper and lower respiratory tract inflammation.

Background Radon-222-enriched hot spring therapy, which is characterized by a safe level of radioactivity, is used for the treatment of rheumatic disorders, and its efficacy has already been studied in several clinical trials. Radon-water inhalation therapy for the treatment of upper and lower airway inflammatory diseases is used in many hot springs centers. However, its application has not been reviewed to date. Methods We systematically searched the PubMed and Scopus databases for clinical trials published in the last 20 years in which objective parameters of upper and lower airway function had been tested before and after radon-enriched inhalation treatment. Results Four prospective studies were found: 1 asthma trial, 1 placebo-controlled chronic rhinosinusitis trial, 1 upper respiratory tract inflammation with nasal obstruction trial, and 1 case-control allergic rhinitis trial. Patients were treated with nasal inhalations of radon-enriched water for 12 to 28 days and were assessed at baseline and after therapy. After 2 weeks of treatment, nasal resistance decreased, flow increased, mucociliary clearance was enhanced, ciliated-to-muciparous cell ratio increased, and %FEV1 increased in asthmatic patients. Conclusion Radon-enriched inhalation therapy improves objective indicators of nasal function in allergic rhinitis and chronic rhinosinusitis, and causes relief of pulmonary obstruction in asthma.

Evaluation of Overground Endoscopy Findings in Sport and Pleasure Horses

Any factors that increase negative pressure in the upper respiratory tract (URT) can influence its mechanics. The aim of this report was to describe the results of URT diagnostic evaluation with overground endoscopy in sport and pleasure horses. The URT and plasma lactate levels were evaluated during rest and during overground endoscopic examination in 19 cases. Horses performed their normal training session. When history and clinical examination suggested a lower airway obstruction, we performed bronchoalveolar lavage. Dorsal displacement of the soft palate (DDSP) was diagnosed in 8 of 19 horses, which might have developed secondary to URT or lower respiratory tract inflammation or obstruction. DDSP was also detected at rest in four cases. Laryngeal hemiplegia (LHP) was diagnosed in 15 of 19 horses, 11 of which were complex cases with other types of URT obstructions. Severe pharyngeal collapse (PHC), suspected already at rest, was visible in two cases during exercise. In contrast, PHC diagnosed with nasal occlusion at rest in two cases was fully compensated under the rider. Plasma lactate levels significantly decreased during exercise. All DDSP cases were suspected to be of inflammatory or obstructive origin, which is different from findings in racehorses, where extrinsic causes are more common. Resting endoscopic examinations were sensitive in cases of obstructive origin. LHP and PHC could not be predicted on the basis of findings at rest, and increased neuromuscular activity during exercise could compensate for the problem in less severe cases. Decreased levels of lactate could be explained by the increased clearance during exercise.

Allergic Respiratory Inflammation and Remodeling.

Asthma and rhinitis are inflammatory diseases of the respiratory tract. Respiratory inflammation of the adaptive and innate immune system is the focus of this review, and chronic inflammation is not limited to the respiratory tissue. The inflammatory response, which consists of phagocytes, eosinophils, mast cells, and lymphocytes, spreads along the respiratory tract, leading to tissue damage. Mast cells and eosinophils are commonly recognized for their detrimental role in allergic reactions on activation through the high- and low-affinity receptors for IgE FcɛRI. These cells rapidly produce and secrete many of the mediators responsible for the typical symptoms of asthma and rhinitis. However, increasing amount of evidence demonstrate that mast cells and leukocytes have vital roles in host defense against pathogenesis. Histological methods are used to study leukocytes and receptor expression pattern in different respiratory tract compartments. The overall aim of this review was to understand the relationship between upper and lower respiratory tract inflammation and remodeling in patients with allergic and non-allergic asthma and rhinitis. In conclusion, this review discusses the relationship between the upper and lower airway in respiratory disease and focuses on the effect of respiratory processes on laryngeal inflammation, remodeling, function, and symptoms; however, they also have a central role in the initiation of the allergic immune response. Our findings suggest that there are differences that contribute to the development of immunopathological mechanisms of these clinically distinct forms of asthma, rhinitis, and chronic obstructive pulmonary disease.

A Recombinant Bacillus Calmette-Guérin (BCG) vaccine promotes protective humoral immunity against the human respiratory syncytial virus

A Recombinant Bacillus Calmette-Guérin (BCG) vaccine promotes protective humoral immunity against the human respiratory syncytial virus

Study of Some Factors Associated with High-Risk Asthma in Children

Background: Bronchial asthma is characterized by lower respiratory tract inflammation associated with bronchial hyper responsiveness with variable and reversible airflow obstruction. The majority of asthmatics are sensitized to at least one common allergen. Aim of the study: The aim of this study is to determine the association of high-risk asthma with allergy-related parameters (total serum IgE levels, serum levels of allergen- specific IgE, eosinophil count, eosinophil percentage ) and pulmonary functions in children. Subjects and methods: 50 Children aged 8-15 years diagnosed with atopic asthma were enrolled in the study. Pulmonary function tests, total leukocyte count (TLC), eosinophil count, and eosinophil percentage were estimated. Total serum immunoglobulin E (IgE) levels and serum IgE levels specific to antigens from 1 to 9 allergens with class 1 or higher, namely, Dermatophagoides pteronyssinus (D. pteronyssinus) , Dermatophagoides farina (D. farina ), cat dander , dog dander, cockroach, egg white, milk, Aspergillus fumigatus, and fish, were measured using UniCAP fluoroenzyme immunoassay (FEIA). Results: This study includes 50 participants, 20 (40%) belonged to the high-risk and 30 (60%) to the low-risk groups. This study revealed no significant association in peak expiratory flow rate (PEFR, ％) values between high-risk and low-risk asthma groups (p ˃ 0.05). There was no significant association in forced expiratory volume in first second [ FEV1 (L)] values between high-risk and low-risk asthma groups ( p ˃ 0.05), whereas there was significant association in FEF 25-75% (forced expiratory flow 25-75%) values between high-risk and low-risk asthma groups ( p ˂ 0.05). There was a significant association between total serum IgE level and high-risk asthma, but TLC, eosinophil count, and eosinophil percentage showed non significant association with high-risk asthma. Serum levels of IgE specific to D. pteronyssinus, D. farina, cat dander, and dog dander were significantly associated with high-risk asthma. The high-risk group had higher serum levels of IgE specific to D. pteronyssinus ( p < 0.0001), D. farina ( p < 0.0001), cat dander ( p < 0.0001), and dog dander antigens ( p < 0.0001) compared with those in the low-risk group. There was no significant association between high-risk asthma and the serum levels of IgE specific to antigens from other allergens (including cockroach, egg white, and milk). Serum levels of IgE specific to Aspergillus fumigatus and fish were both negative (class level < 1) in both the high-risk group and the low-risk group. Conclusion Children with higher serum levels of IgE specific to D.pteronyssinus, D. farina, cat dander and dog dander antigens, and total serum IgE levels, and lower FEF25-75% values belong to the high-risk asthma group. The characterization of risk factors has enabled us to identify high-risk asthma in children , leading to better treatment options.

Effects of a single dose of enrofloxacin on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation

To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. 32 healthy Thoroughbreds. All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hour before being transported 1,210 km via commercial vans (duration, approx 26 hours). Before and after transportation, clinical examination, measurement of temperature per rectum, and hematologic analysis were performed for all horses; a tracheobronchial aspirate was collected for neutrophil quantification in 12 horses (6/group). Horses received antimicrobial treatment after transportation if deemed necessary by the attending clinician. No adverse effects were associated with treatment. After transportation, WBC count and serum amyloid A concentration in peripheral blood samples and neutrophil counts in tracheobronchial aspirates were significantly lower in horses of the enrofloxacin group than in untreated control horses. Fever (rectal temperature, ≥ 38.5°C) after transportation was detected in 3 of 16 enrofloxacin group horses and 9 of 16 control horses; additional antimicrobial treatment was required in 2 horses in the enrofloxacin group and 7 horses in the control group. In horses premedicated with interferon-α, enrofloxacin appeared to provide better protection against fever and lower respiratory tract inflammation than did saline solution.

Saccharomyces boulardii w profilaktyce biegunki związanej z antybiotykoterapią – doświadczenia własne

IntroductionSaccharomyces boulardii has documented clinical activity in the prevention and treatment of diarrhea associated with antibiotic therapy in children and adults. AimThe aim of the study was to evaluate the incidence of loose stools and/or increased their number in patients who received S. boulardii during antibiotic therapy and comparison with results of other published studies on this topic. Patients and methodsObservational data were evaluated from 130 patients aged 3 mth.–17.5 years who received S. boulardii (250–500 mg per day) during antibiotic therapy. The occurrence of loose stools and/or increased their numbers per day, which occurred de novo in the course of antibiotic therapy was analyzed. Antibiotic therapy was used in patients with upper and lower respiratory tract inflammation – the group I (n=83) and during Helicobacter pylori eradication – the group II (n=47). In group I, there were 18 infants and 65 children over 12 months. The most commonly used antibiotics for patients with respiratory tract infection (group I) were: amoxicillin with clavulanic acid (n=39) and cefuroxime (n=21). In the eradication of Helicobacter pylori amoxicillin and metronidazole were used – group II. ResultsLoose stools and/or increased their number on any day of observation occurred in 18 patients of group I (21.68%) and 6 patients in group II (12.76%), but only in 11.5% of the whole analyzed group symptoms occurred 48 hours or longer, 14.46% in group I and 6.38% in group II. The total number of days with problems in each group was: group I – 43 of 757 (5.68%), group II – 10 of 470 (2.12%). Only in 4 (3.07%) patients symptoms occurred for longer than three days. Average number of days with symptoms was: 2.38 days in the group I, 1.8 days – in group II. More often, symptoms lasting 48 hours or more was observed in treated with cefuroxime – 19.05% (n=7), than in patients treated with amoxicillin with clavulanic acid – 7.69% (n=3). In the group I loose stools and/or increased their number occurring for 48 hours or longer were more frequent in infants (27.78%) compared to children aged above 12 months of life (10.77%). There was no patient in whom antibiotic therapy was discontinued because of occurrence of loose stools and/or increase their numbers. ConclusionSaccharomyces boulardii is effective in preventing diarrhea associated with antibiotic therapy.

Role and mechanism of the expression of matrix metalloproteinase 9 and tumor necrosis factor α in upper and lower respiratory tract inflammation in rats

To investigate the role and mechanism of matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma(AS). The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining (SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were (154.8 ± 12.0) and (124.0 ± 8.2), (43.2 ± 7.6) and (34.5 ± 5.0) in the control groups, the difference was significant (t value were 24.260, 29.525 respectively, all P < 0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9 ± 11.7) and (120.1 ± 7.3), (48.6 ± 7.6) and (39.1 ± 5.2) in control groups, the difference was significant (t value were 22.929 and 28.530 respectively, all P < 0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8 ± 17.0), and (134.8 ± 7.9), (57.6 ± 23.3) and (40.3 ± 8.2) in control groups, the difference was significant (t value were 13.836 and 26.220, all P < 0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179.2 ± 15.4) and (153.5 ± 10.1), (70.5 ± 33.1) and (33.8 ± 14.0) in control groups, the difference was significant (t value were 9.412 and 21.858, all P < 0.05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR (r values were 0.893 and 0.700 respectively, P values were 0.001 and 0.024, respectively) and AS (r values were 0.692 and 0.644 respectively, P values were 0.027 and 0.044 respectively) groups. The inflammation is similar between AR and AS. The MMP-9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.

Ventilator-associated Tracheobronchitis

The incidence of ventilator-associated tracheobronchitis (VAT) varies from 10% to 16.5% of intubated critically ill patients. This infection represents an intermediate process between lower respiratory tract colonization and ventilator-associated pneumonia (VAP). VAT definition is still controversial. However, the most specific definition includes all the following criteria: fever (>38°C) with no other recognizable cause, purulent sputum production, positive culture of a respiratory specimen at significant threshold concentrations, and no radiographic signs of a new pneumonia. This infection is frequently caused by Pseudomonas aeruginosa, and is characterized by lower respiratory tract inflammation and increased sputum production resulting in weaning difficulties and longer duration of mechanical ventilation. Two recent randomized trials reported beneficial effects of antimicrobial therapy in patients with VAT. In a randomized blinded placebo-controlled trial, aerosolized antibiotics significantly reduced the incidence of subsequent VAP. Further, aerosolized antibiotics increased weaning from mechanical ventilation, reduced usage of systemic antibiotics, and antibiotic resistance. The impact of systemic antibiotics on outcomes of VAT patients was evaluated in a randomized unblinded controlled study. Antibiotic treatment increased mechanical ventilation-free days, and reduced the incidence of subsequent VAP and intensive care unit mortality. The beneficial effects of antibiotic treatment in VAT patients should be confirmed, and the best duration of antimicrobial therapy should be determined by future studies.

Nosocomial tracheobronchitis

Nosocomial tracheobronchitis is common among intubated critically ill patients. Ventilator-associated tracheobronchitis (VAT) represents an intermediate process between lower respiratory tract colonization and ventilator-associated pneumonia. The aim of this review is to discuss recent findings on VAT. VAT is defined using all the following criteria: fever (>38 degrees C) with no other recognizable cause, purulent sputum production, positive culture of respiratory specimen at significant threshold, and no radiographic signs of new pneumonia. This infection is frequently caused by Pseudomonas aeruginosa and characterized by lower respiratory tract inflammation and increased sputum production resulting in weaning difficulties and longer duration of mechanical ventilation. The effect of aerosolized antibiotics on outcomes in VAT patients was evaluated in a randomized blinded placebo-controlled trial. Aerosolized antibiotics significantly increased weaning from mechanical ventilation and reduced subsequent ventilator-associated pneumonia and usage of systemic antibiotics and antibiotic resistance. A randomized unblinded controlled study assessed the impact of systemic antibiotics on outcome of VAT patients. Antibiotic treatment increased mechanical ventilation-free days and reduced the incidence of subsequent ventilator-associated pneumonia and ICU mortality. Antibiotic treatment is beneficial in VAT patients. Future studies should confirm these promising results and determine the best duration of antimicrobial therapy in these patients.

Role of human neutrophil peptides in lung inflammation associated with alpha1-antitrypsin deficiency.

Individuals with alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for early-onset destructive lung disease as a result of insufficient lower respiratory tract alpha(1)-AT and an increased burden of neutrophil products such as elastase. Human neutrophil peptides (HNP), the most abundant protein component of neutrophil azurophilic granules, represent another potential inflammatory component in lung disease characterized by increased numbers of activated or deteriorating neutrophils. The purpose of this study was to determine the role of HNP in lower respiratory tract inflammation and destruction occuring in alpha(1)-AT deficiency. alpha(1)-AT-deficient individuals (n = 33) and healthy control subjects (n = 21) were evaluated by bronchoalveolar lavage. HNP concentrations were significantly higher in alpha(1)-AT-deficient individuals (1,976 +/- 692 vs. 29 +/- 12 nM, P < 0.0001), and levels correlated with markers of neutrophil-mediated lung inflammation. In vitro, HNP produced a dose-dependent cytotoxic effect on alveolar macrophages and stimulated production of the potent neutrophil chemoattractants leukotriene B(4) and interleukin-8 by alveolar macrophages, with a 6- to 10-fold increase in chemoattractant production over negative control cultures (P < 0.05). A synergistic effect was noted between HNP and neutrophil elastase with regard to leukotriene B(4) production. Importantly, the proinflammatory effects of HNP were blocked by alpha(1)-AT. HNP likely play an important role in amplifying and maintaining neutrophil-mediated inflammation in the lungs.

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco.

Cigarette smoking remains a major public health problem. For smokers who cannot or do not wish to quit, few options exist to reduce health risks. A cigarette-like nicotine delivery device that heats rather than burns tobacco might deliver nicotine with fewer toxins. The current study was designed to determine whether asymptomatic heavy smokers who did not wish to quit had improvement in lower respiratory tract inflammation after switching to Eclipse, a cigarette-like nicotine delivery device that primarily heats rather than burns tobacco. Twelve smokers of at least 40 cigarettes daily, asymptomatic and in good health, underwent paired bronchoscopies, bronchoalveolar lavages and endobronchial biopsies before and after 2 months of using Eclipse. Eight normal non-smoking individuals were evaluated on one occasion for comparison. Inflammation was assessed by direct inspection and by cytological parameters. Goblet cell metaplasia was assessed histologically. Compared to non-smokers, smokers had increased visible inflammation, increased recovery of inflammatory cells and increased percentage of goblet cells. There were significant reductions in all these parameters following a switch to Eclipse use, although the improvement did not reach the normal range. No significant differences were observed in peripheral blood measures. Nicotine levels were generally maintained, and exhaled carbon monoxide (CO) levels trended strongly upward. One individual experienced a transient twofold increase in CO and concurrently experienced transient headaches. Eclipse use may be a strategy to reduce the health risks for heavy smokers unwilling or unable to quit.