Invasive Aspergillus Pseudomembranous and Obstructive Tracheo-bronchitis in an Immuno-competent Patient.

A 19 year female, presented with life threatening haemoptysis and cough with minimum expectoration for 3 months. Bronchoscopy showed multiple nodules in airway. The direct microscopy and culture of sputum revealed fungal elements and Aspergillus flavus respectively. Serum Galactomannan was positive. Thus diagnosis of invasive aspergillus tracheo-bronchitis made. She responded to voriconazole. Aspergillus tracheo-bronchitis is a rare form of invasive pulmonary aspergillosis in immuno-competent host. Aspergillus spp in respiratory samples should not be routinely discarded as colonization.

[CYCLIC VARIATIONS OF LARYNGOTRACHEITIS IN CHILDREN].

It was analyzed the incidences of laryngotracheitis (LT) in children aged 0 to 14 years in Vinnytsya between 1995 and 2008. It was studied seasonal and circadian rhythms of LT in children. The seasonal variations of LT are characterized by two-wave curve with peaks in October and March, and with a significant decrease in July and August. The incidences of LT in October and March exceed the incidences of LT in July and August in 2.6 times. Circadian variation of LT is characterized by peak at night. The incidences of LT at night exceed the incidences in the morning in 2.6 times. The total number of the incidences of LT in the evening and at night exceed the total number of the incidences of LT in the morning and in the afternoon in 1.7 times. The maximum of incidences of LT to minimum of incidences of LT per hour ratio is 5:1 in girls compared to 4:1 in boys.

[SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study.

Antibiotic treatment of ventilator-associated tracheobronchitis: to treat or not to treat?

PURPOSE OF REVIEW: To evaluate the data on antimicrobial therapy for ventilator-associated tracheobronchitis (VAT) to prevent ventilator-associated pneumonia (VAP), and its impact on patient outcomes. RECENT FINDINGS: Mechanically ventilated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to VAT and/or VAP. Previous studies suggest that 10-30% of patients with VAT progress to VAP, which results in increased morbidity but not mortality. Several natural history studies and small randomized controlled trials and a meta-analysis reported that appropriate, pre-emptive antibiotic treatment for VAT reduces VAP, duration of intubation and length of ICU stay. SUMMARY: This review focuses on diagnostic criteria for VAT and VAP, etiologic agents, rationale and benefits of initiating pre-emptive, appropriate antibiotic treatment for VAT to prevent VAP, improve patient outcomes and associated acute and chronic healthcare costs.

Outcomes associated with ventilator-associated events (VAE), respiratory infections (VARI), pneumonia (VAP) and tracheobronchitis (VAT) in ventilated pediatric ICU patients: A multicentre prospective cohort study.

OBJECTIVES: An objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ventilator-associated events (VAE) are limited to surveillance purposes. RESEARCH METHODOLOGY/DESIGN: This was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day. SETTING: 15 Paediatric Intensive Care Units. MAIN OUTCOME MEASURES: Mechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality. RESULTS: A cohort of 391 ventilated children with an age (median, [Interquartile Ranges]) of 1 year[0.2-5.3] and 7 days[5-10] of mechanical ventilation were included. Intensive care and hospital stays were 11 [7-19] and 21 [14-39] days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively. CONCLUSION: When assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis. IMPLICATIONS FOR PRACTICE: Incorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.

Effects of Lung Support Formula on respiratory symptoms among older adults: results of a three-month follow-up study in Shanghai, China.

BACKGROUND: With the acceleration of industrialization in low or middle-income nations, the prevalence of respiratory symptoms among older adults is even more significant now in China. Contemporary treatments using Western medicine, such as anti-inflammatory regimens, may be effective in relieving the symptoms, but may have unexpected side effects. Some natural products may be effective in improving respiratory functions, yet their efficacies remain to be examined in randomized, placebo-controlled studies. To evaluate the effects of Lung Support Formula, a nutritional supplement which contains naturally derived Chinese herbal medicines, we conducted a clinical study among older adults in Shanghai, China. METHODS: A total of 100 patients over 50 years old were recruited and blindly randomized into the treatment or control group. The subjects took either 1 Lung Support Formula capsule or a placebo capsule twice a day for 12 weeks. All subjects were followed-up every 4 weeks to perform investigative and clinical examinations. Repeated measure of analysis of variance was employed to compare the trend of respiratory symptoms scores between the 2 groups during 12 weeks of follow-up. RESULTS: Fifty patients from the treatment group and 49 patients in the control group completed the 3-month follow-up. No adverse events were reported in the treatment duration. The percentage of patients reported to have chronic cough, chronic expectoration and chronic bronchitis were significantly decreased in the treatment group when compared with baseline after a 3-month intervention (P < 0.05). The respiratory symptoms scores declined gradually with the lapse of time (P < 0.05) in the treatment group and there were no significant changes in the control group by repeated measure of analysis of variance (P > 0.05). CONCLUSIONS: The clinical research shows that use of Lung Support Formula shows significant improvements of respiratory symptoms and is well-tolerated in short-term use among older adults. An additional study involving more subjects and longer-term follow-up would be needed to provide convincing evidence of the improvement of respiratory symptoms in the treatment group.

An unusual case of invasive Aspergillus ulcerative tracheobronchitis without involvement of lung parenchyma in a post-renal transplant patient.

We present the case of a 54-year-old male, who presented with respiratory complaints four months after he underwent renal transplantation. Bronchoscopy showed ulcerated mucosa of the left main bronchus and computed tomography (CT) of the thorax showed foci of air within the bronchial wall. A biopsy from the lesion showed septate fungal hyphae, dichotomously branching at acute angles. A locally invasive Aspergillus ulcerative tracheobronchitis with no parenchymal involvement is an important cause of tracheobronchitis in post-renal transplant patients. An early diagnosis and institution of appropriate treatment can improve the outcome. A combination treatment of caspofungin and voriconazole can be considered if patient is not responding to voriconazole alone.

Allergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation.

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I (sc)) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I (sc), while a much larger increase was observed following basolateral AP addition. In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTR(inh)172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels' (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

Effects of clarithromycin and dexamethasone on mucus production in isografted rat trachea.

OBJECTIVES: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. METHODS: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. RESULTS: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. CONCLUSIONS: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

The Tricky Trachea: Tracheitis and Mediastinitis Treated With Infliximab and Steroids in a Patient With Ulcerative Colitis.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

Pulmonary Manifestations of Inflammatory Bowel Disease.

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.

Bacterial tracheitis in pediatrics: 12 year experience at a medical center in Taiwan.

BACKGROUND: Bacterial tracheitis may cause life-threatening airway obstruction. METHODS: Records of patients admitted to the pediatric wards of Mackay Memorial Hospital between 1994 and 2005 with a diagnosis of bacterial tracheitis made on bronchoscopic visualization of thick membranous tracheal secretions were retrospectively reviewed. RESULTS: A total of 40 patients (aged 1 month-8 years, 29 [73%] under 3 years old) were included. Cough, fever, dyspnea, and hoarseness were the commonest symptoms. Fourteen patients (21%) required intubation. The most frequently isolated bacteriae were alpha-hemolytic streptococcus (in 11, 38%), pseudomonas (5, 17%), and Staphylococcus aureus (4, 14%). Intubation was more frequent in patients seen between 1994 and 1999 compared with those seen later (8/12 early vs 9/28 late). In the early period alpha-hemolytic streptococcus (55%) and pseudomonas (36%) were isolated. In the later period the most frequently isolated bacteria was alpha-hemolytic streptococcus (28%), followed by S. aureus (22%). No patients died, but those with pseudomonas infection had more severe complications, including tracheal stenosis. The average hospital stay in the early period was 26.2 +/- 20.5 days versus 9.1 +/- 4.8 days in the late period. The corresponding lengths of stay in the intensive care unit were 10.5 +/- 11.5 days and 2.0 +/- 2.2 days. CONCLUSIONS: Bacterial tracheitis requiring hospitalization of children appeared to be milder in the second half of the study period. Pseudomonas tracheitis tends to have a severe course.

Bacterial tracheitis--not always primary.

A child presented with features of bacterial tracheitis with complete response to therapy. He presented with a recurrence one week later. A foreign body in the tracheal wall was diagnosed and removed by bronchoscopy. Tracheal intubation for airway management and tracheal toileting are not enough in bacterial tracheitis; bronchoscopy should be considered to diagnose any underlying cause.

[Some mechanisms of a recurrent course of stenosing laryngotracheitis in children].

Staged development of dysbiotic disturbance of the upper airways was revealed in children suffering from stenosing laryngotracheitis in the presence of viral infection. Chronic persistent virus-bacterial inflammation of respiratory tract mucosa and resultant hypersensitivity of the airways produce chronic defects in lung ventilation in patients with recurrent stenosing laryngotracheitis. High sensitivity of the airways to histamine is related to bioelectric activity of the brain characterized by dominant irritation of the mesencephalo-diencephalic structures. Typical features of the curve flow-volume and paradoxic result of the test with broncholytic drugs verified tracheobronchial dyskinesia in patients with stenosing laryngotracheitis. Such dyskinesia promoted the recurrent disease with transformation into bronchial asthma.

Effect of needle puncture and electro-acupuncture on mucociliary clearance in anesthetized quails.

BACKGROUND: Acupuncture therapy for obstructive respiratory diseases has been effectively used in clinical practice and the acupuncture points or acupoints of Zhongfu and Tiantu are commonly-used acupoints to treat patients with the diseases. Since the impaired mucociliary clearance is among the most important features of airway inflammation in most obstructive respiratory diseases, the effect of needle puncture and electro-acupuncture at the specific acupoints on tracheal mucociliary clearance was investigated in anesthetized quails. METHODS: Mucociliary transport velocity on tracheal mucosa was measured through observing the optimal pathway, and fucose and protein contents in tracheal lavages were determined with biochemical methods. In the therapeutic group, needle puncture or electro-acupuncture stimulation to the acupoints was applied without or with constant current output in 2 mA and at frequency of 100 Hz for 60 minutes. In the sham group, electro-acupuncture stimulation to Liangmen was applied. RESULTS: Our present experiments demonstrated that the electro-acupuncture stimulation to Zhongfu and Tiantu significantly increased tracheal mucociliary transport velocity and decreased the content of protein in the tracheal lavage, compared with the control group. Moreover, either needle puncture or electro-acupuncture stimulation to Zhongfu and Tiantu significantly reverted the human neutrophil elastase-induced decrease in tracheal mucociliary transport velocity and human neutrophil elastase -induced increase in the contents of fucose and protein in the tracheal lavage, compared with the control group. CONCLUSION: These results suggest that either needle puncture or electro-acupuncture stimulation to the effective acupoints significantly improves both airway mucociliary clearance and the airway surface liquid and that the improvements maybe ascribed to both the special function of the points and the substantial stimulation of electricity.

Antiprotease function of airway secretions in purulent tracheobronchitis.

STUDY OBJECTIVES: Unopposed activity of the serine protease, human leukocyte elastase (HLE), is detectable in the airways of patients with purulent tracheobronchitis. The aim of this study was to assess the compartmentalization of HLE activity in the liquid sol phase and the solid gel phase of airway secretions. DESIGN: Seventy samples of tracheobrochial aspirates were obtained from patients who had hypersecretion and were receiving mechanical ventilation. METHODS: Samples were separated into sol and gel ("mucous pellet") phases, and HLE activity was measured using chromogenic substrate degradation. HLE was eluted from the mucous pellet using hypertonic saline solution, 1 mol/L, or bovine pancreatic deoxyribonuclease (DNase), 16 micromol/L. RESULTS: HLE activity partitioned between the sol and gel phases of the secretions, with most of the activity present in the gel phase (32:1 ratio of gel to sol HLE activity). The activity of HLE was 95% inhibited when bound to the gel phase, but activity appeared to be largely restored after elution from the gel phase. The gel phase was capable of binding additional exogenous HLE, and its binding capacity for exogenous HLE was not saturated by concentrations that exceeded the highest clinically relevant HLE levels (1.1 mg/mL). Hypertonic saline solution and DNase I efficiently liberated endogenous and exogenous gel phase-bound HLE activity, suggesting that electrostatic bonds and DNA, respectively, play important roles in binding HLE to the gel phase. CONCLUSIONS: The solid phase of airway secretions is a more important modulator of elastase-antielastase balance than has been previously recognized.

The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.

1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetized rats. 2. Bradykinin increased the amount of plasma (fluorimetric assay for protein) in the perfusate (response; 10.98 +/- 0.357 microliters, n = 69; total increase in plasma over basal during 45 min after start of bradykinin application) and 2 responses at a 90 min interval were reproducible. Carbon labelling was seen in tracheal sections from animals that received i.v. colloidal carbon, indicating that bradykinin caused tracheal microvessels to leak (increase in microvascular permeability). 3. Five minutes after topical formoterol, 5 or 30 nmol (10 or 60 microM perfused for 5 min), the bradykinin response was significantly reduced. The effects of formoterol were not dose-related, i.e. were maximal at 5 nmol. The bradykinin response was at control levels 30 min after 5 nmol formoterol. After 30 nmol formoterol, the response was still reduced 120 min later. The bradykinin response was significantly reduced 60 min after systemic formoterol (i.p., 0.029 to 870 nmol kg-1) and, for 290 nmol kg-1 i.p. formoterol, this reduction was shown to last at least 150 min. 4 The bradykinin response was not prevented by supramaximal doses of topical (30 nmol) or i.p.(870 nmol kg-1) formoterol and carbon-labelled microvessels were seen in tracheal sections from all animals that received formoterol, although these were less in number and less densely labelled than in the absence of formoterol. There was a correlation between the plasma exudation response (ul) and the number of carbon-labelled vessels (Spearman's correlation coefficient 0.415, P<0.001).5 In animals pretreated with propranolol (3 pmol kg-1, i.v.), 29 nmol kg-1 formoterol, i.p., did not reduce the bradykinin response. However, propranolol itself markedly potentiated the bradykinin response which confounded the interpretation of its effects on formoterol.6 The study has shown, in a preparation of rat trachea in situ, that supramaximal doses of the beta2-adrenoceptor agonist, formoterol (a) produced a sustained, but incomplete, inhibition of plasma exudation (induced by topical bradykinin), and (b) did not prevent bradykinin-induced leaky microvessels. The data support the view that, at least in rodent airways, beta2-adrenoceptor agonists attenuate, but do not abolish, the microvascular permeability effects of bradykinin, a putative asthma mediator.

The measurement of thoraco-abdominal asynchrony in infants with severe laryngotracheobronchitis.

Retractions of the lower ribcage (chest wall distortion [CWD]) during inspiration are frequently observed with moderate to severe respiratory disease in the infant. Laryngotracheobronchitis (LTB) results in a reversible partial airway obstruction with severe CWD. We wished to measure the motion of the chest wall during distortion to determine the changes in minute ventilation (VE) and to evaluate this clinical sign as a means of assessing disease severity. The respiratory inductance plethysmograph was used to determine the distortion of the lower chest wall, and distortion was correlated with VE, measured at the mouth, in six infants with severe LTB and ventilatory failure. As the conditions of these infants improved, the CWD decreased with decreasing transcutaneous carbon dioxide tension (tcPCO2), VE increased from 0.27 +/- 0.12 L.min-1 x kg-1 at a tcPCO2 of 64 mm Hg to 0.64 +/- 0.06 L.min-1 x kg-1 when the tcPCO2 had fallen to 28 mm Hg. Over the same change in tcPCO2, the tidal volume (VT) increased from 4.8 +/- 0.5 ml.kg-1 to 15.7 +/- 1.4 ml.kg-1. In the most severe disease state, the excursion of the chest wall (as an inductance) was -14 +/- 3 mV in severe obstruction, but increased to 75 mV +/- 4 mV with resolution of the illness. The timing and vector of movement of the abdomen and chest wall were expressed as a Lissajous figure, which is measured as a phase angle. The severity of the disease process, as determined by tcPCO2 was directly related to the phase relationship, and thus reflected both VE and VT. The severity of the CWD may be assessed rapidly by the use of Lissajous figures.

Inhibition of neutral endopeptidase potentiates neurogenic inflammation in the rat trachea.

The present study was performed to determine whether neurogenic inflammation in the rat trachea can be exaggerated by inhibiting neutral endopeptidase, an enzyme that degrades tachykinins that are believed to mediate neurogenic inflammation. Neurogenic inflammation was produced by antidromic electrical stimulation of one vagus nerve (2.5 Hz, 1 ms, 5 V for 5 min) in the presence of atropine or by an intravenous injection of capsaicin (100 micrograms/kg). Neutrophils that adhered to the endothelium of venules were visualized and counted in tracheal whole mounts that were stained by a histochemical reaction for myeloperoxidase. Neural inflammation increased the number of adherent neutrophils. Pretreatment with the neutral endopeptidase inhibitor phosphoramidon (1.0 or 2.5 mg/kg iv) increased neutrophil adhesion induced by neural inflammation. As assessed by the amount of extravasation of Monastral blue pigment, neural inflammation also increased vascular permeability, and this change was potentiated by phosphoramidon. These results are consistent with the concept that neuropeptides released from sensory nerves in the tracheal mucosa cause neutrophils to adhere to venules and increase vascular permeability and that these effects are modulated by neutral endopeptidase.