Interaction of genotype and environment results in a specific phenotype of the clinical course of asthma. TGFβ-1 gene belongs to the important group of genes involved in the regulation of proliferation, differentiation, adhesion, and migration of a variety of cell types. TGFβ-1 is inhibitory for B and T cells, as well as IgE production. In particular, it is engaged in inflammation of the bronchi and airway remodeling in asthma, which processes are critical in the pathogenesis of the disease. The aim of this study was to evaluate the correlation between the level of expression of TGFβ-1 and the severity of asthma.The study included 39 participants (20 healthy subjects and 19 patients with asthma). Each sample was analysed by using real time PCR.There was statistical associations between the control group and the group of patients (p = 0,00007). It was demonstrated strong correlation between healthy and patients with severe asthma according GINA guidelines (p = 0,017). It was found the strong statistical correlation between healthy and patients with severe corticosteroid dependent asthma (p = 0,013). Correlations were observed between levels of asthma severity according to the ATS guidelines and controls. The influence of the level of TGFβ-1 mRNA expression and the severity of asthma (ATS) in the FEV1 (%) parameter value was found.It was found that an important role is played by TGFβ-1 in the pathogenesis of asthma.

: Treatment options for central airway tumors include surgery, radiotherapy, and in those with inoperable or emergent airway obstruction, therapeutic bronchoscopy. Herein, we report our experience with the exclusive use of rigid bronchoscope in the management of central airway tumors.: Retrospective review of charts of patients who underwent rigid bronchoscopy and mechanical coring for the management of central airway (trachea and mainstem bronchi) tumors over a period of 2 years. "Successful" outcome was defined as procedure leading to reduction of luminal obstruction to <50% and improvement of respiratory distress. "Unsuccessful" outcome was defined in cases where the luminal obstruction could not be reduced by ≥50% or there was lack of improvement in the clinical status of the patient.: During the study period, 30 patients with symptomatic central airway tumors were encountered. Of these, 23 patients underwent 31 rigid bronchoscopic procedures. Respiratory failure was present in 15 (65.2%) patients. Adenoid cystic carcinoma was the most common primary tracheal tumor, whereas squamous cell carcinoma was the most common secondary tracheobronchial tumor. The procedure was successful in 19 (82.6%) patients. Complications were encountered in 10 of the 31 (32.3%) rigid bronchoscopies. There was no procedural mortality.: Rigid bronchoscopy and mechanical debulking as a sole therapy is an effective and safe procedure for airway obstruction resulting from tracheobronchial tumors.

PURPOSE:

This study was performed to objectively evaluate the effect of high-dose-rate endobronchial brachytherapy (HDREB) in symptom palliation of patients with malignant airway obstruction and treatment-related toxicity.

METHODS AND MATERIALS:

Seventy-eight patients were treated with palliative intent according to a prospective observational protocol. HDREB was delivered in three fractions of 7.5 Gy at weekly or fortnightly intervals, associated or not with external beam irradiation. Most patients presented with lung cancer primaries and were treated because of lesions located in the trachea and/or main bronchi. Performance status, degree of obstruction, and symptom palliation were graded according to an objective score index, defined before and after HDREB at the last followup visit. Survival was considered from the end of HDREB for at least 3 years or until death.

RESULTS:

Overall, there was a 70% improvement, with migration of patients from lower to higher performance status. Bronchial obstruction was improved in 73.4% of the patients. The symptom that presented the better response was hemoptysis (100% complete relief) followed by postobstructive pneumonia (80%), dyspnea (57.4%), and cough (33.9%). Median survival was 6 months and improved in patients with complete response at bronchoscopy (9 months). There were two (2.6%) cases of bronchial fistulae and eight cases (10.2%) of fatal hemoptysis.

CONCLUSIONS:

HDREB is an excellent modality for palliating malignant airway obstruction resulting in quality of life improvement, with a good tolerance, patient compliance, and low rate of complications.

BACKGROUND AND OBJECTIVE:

Microdebrider bronchoscopy is a relatively new modality for the management of central airway obstruction (CAO) of both benign and malignant origin. Our objective was to describe our experience with this technique, with special attention to its safety and effectiveness.

METHODS:

We retrospectively reviewed cases of therapeutic bronchoscopies using microdebrider for CAO from two institutions (M.D. Anderson Cancer Center and Michael E. Debakey VA Medical Center, Houston) from August 2008 through February 2012.

RESULTS:

We identified 51 cases. Malignant CAO was detected in 36 cases (71%): NSCLC (n=22), melanoma (n=3), SCLC (n=2), thyroid cancer (n=2), esophageal carcinoma (n=2), breast cancer (n=2), and others (n=3). Benign diseases included: papillomas (n=8), granulation tissue (n=3), and others (n=4). Obstruction was purely endoluminal in 32 cases (63%). Pre-treatment obstruction was severe in 25 cases (49%), moderate in 20 cases (39%) and mild in 6 (12%). Lesions were located in the trachea (n=23), main stem bronchi (n=25), and bronchus intermedius (n=8), with some patients having more than one lesion. After tumor debulking with microdebrider, the residual airway obstruction was insignificant (n=27 cases; 53%), mild (n=23 cases; 45%), and moderate (n=1; 2%). No major complications were encountered, only 2 patients had mild adverse events: one case of pneumomediastinum, and one self-expandable stent damage requiring its removal. Two patients (4%) died within 30 days of causes unrelated to the procedure or the CAO.

CONCLUSIONS:

Microdebrider bronchoscopy is a potentially safe and effective way to manage central airway obstruction of both malignant and benign origin.

Previous reports have described structural airway abnormalities in children with non-cystic fibrosis chronic suppurative lung disease as well as obliterative membranes in the major bronchi of cystic fibrosis patients. The putative paradigm proposed in the evolution of these membranes invokes intense inflammation resulting in granulation tissue and neovascularization with the formation of pyogenic granuloma and eventually fibrosis. Our series of four cases widens the spectrum of conditions that may be conducive to large airway obliteration to include non-suppurative chronic infections and possibly immunosuppression. Obliteration of lumina in proximal and distal airways was visualized on bronchoscopy, the latter by the use of the ultrathin bronchoscopes. An attempt at invasive intervention by transbronchial breaching of the obstruction was unsuccessful in three cases, and in one case, the obliterative process resolved spontaneously and without any radiologic trace, presumably by resorption or rupture or through development of collateral ventilation. This series highlights the use of bronchoscopy for diagnosis and occasionally for therapeutic intervention in hitherto little recognized obliterative airway lesions. These acquired obliterative lesions should be considered in the evaluation of patients with isolated non-resolving pulmonary infiltrates or other conditions in which bronchial and bronchiolar patency may be impaired. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.

(-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.

BACKGROUND::

Tyrosine (Tyr) kinases and mitogen-activated protein kinases have been thought to participate in the contractile response in various smooth muscles. The aim of the current study was to investigate the involvement of the Tyr kinase pathway in the contraction of bronchial smooth muscle.

METHODS::

Ring preparations of bronchi isolated from rats were suspended in an organ bath. Isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine the phosphorylation of c-Jun N-terminal kinasess (JNKs) in bronchial smooth muscle.

RESULTS::

To examine the role of mitogen-activated protein kinase(s) in bronchial smooth muscle contraction, the effects of MPAK inhibitors were investigated in this study. The contraction induced by carbachol (CCh) was significantly inhibited by pretreatment with selective Tyr kinase inhibitors (genistein and ST638, n = 6, respectively), and a JNK inhibitor (SP600125, n = 6). The contractions induced by high K depolarization (n = 4), orthovanadate (a potent Tyr phosphatase inhibitor) and sodium fluoride (a G protein activator; NaF) were also significantly inhibited by selective Tyr kinase inhibitors and a JNK inhibitor (n = 4, respectively). However, the contraction induced by calyculin-A was not affected by SP600125. On the other hand, JNKs were phosphorylated by CCh (2.2 ± 0,4 [mean±SEM] fold increase). The JNK phosphorylation induced by CCh was significantly inhibited by SP600125 (n = 4).

CONCLUSION:

: These findings suggest that the Tyr kinase/JNK pathway may play a role in bronchial smooth muscle contraction. Strategies to inhibit JNK activation may represent a novel therapeutic approach for diseases involving airway obstruction, such as asthma and chronic obstructive pulmonary disease.

We describe the case of a previously well young man who presented acutely to hospital with a history of progressive chest symptoms and systemic upset. At admission, clinical evidence of left upper lobe collapse on respiratory examination and chest x-ray gave rise to significant clinical concern. Initial assessment by CT suggested a possible aspirated foreign body in the left upper lobe bronchus with distal left upper lobe collapse. Subsequent rigid bronchoscopy identified a solid abnormality totally occluding the left upper lobe bronchus, which did not appear to be a foreign body. The patient became progressively more unwell with clinical signs of chest sepsis and failed to settle with medical therapy. A decision was made to undertake a lobectomy to remove the collapsed lobe and obstructing endobronchial lesion. Histology confirmed that the cause of bronchial obstruction was a mesenchymoma (pulmonary hamartoma).

Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of remodelling, peribronchiolar fibrosis is observed in the small airways of patients with COPD and contributes to airway obstruction. Epithelial to mesenchymal transition (EMT) appears to be involved in the formation of peribronchiolar fibrosis. This study examines the EMT process in human bronchial epithelial cells (HBECs) from non-smokers, smokers and patients with COPD as well as the in vitro effect of cigarette smoke extract (CSE) on EMT.HBECs from non-smokers (n=5), smokers (n=12) and patients with COPD (n=15) were collected to measure the mesenchymal markers α-smooth muscle actin, vimentin and collagen type I and the epithelial markers E-cadherin, ZO-1 and cytokeratin 5 and 18 by real time-PCR and protein array. In vitro differentiated bronchial epithelial cells were stimulated with CSE.Mesenchymal markers were upregulated in HBECs of smokers and patients with COPD compared with non-smokers. In contrast, epithelial cell markers were downregulated. In vitro differentiated HBECs underwent EMT after 72 h of CSE exposure through the activation of intracellular reactive oxygen species, the release and autocrine action of transforming growth factor β1, the phosphorylation of ERK1/2 and Smad3 and by the downregulation of cyclic monophosphate.The EMT process is present in bronchial epithelial cells of the small bronchi of smokers and patients with COPD and is activated by cigarette smoke in vitro.

Bronchiectasis is a complex pathological endpoint arrived at through a diverse interplay between lung infection and altered immune function. It comprises irreversible, abnormal dilatation of one or more bronchi, with chronic airway inflammation and is associated with recurrent chest infections, airflow obstruction, chronic cough, excessive sputum production, and malaise. Many pathogens are associated with this disease, including chronic bacterial infections, nontuberculous mycobacteria, and aspergillis. However, the etiology is poorly defined. Disease-associated genes indicate a likely contribution to disease mechanism both from innate and adaptive immunity. The role of immune mechanisms is highlighted by the occurrence of bronchiectasis in a subset of patients with rheumatoid arthritis or inflammatory bowel disease as well as diseases of immune dysregulation such as combined variable immune deficiency, transporter associated with antigen processing (TAP) deficiency syndrome, and hyper-IgE syndrome. Recent evidence indicates a possible role of excessive natural killer cell activation in pathogenesis.