Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6%) and II (21.6 ± 17.8%), but not in group III (2.7 ± 15.3%). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1%) and II (37.4 ± 27.1%), but not in group III (19.0 ± 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Prenatal tracheal ligation or intra-amniotic administration of surfactant or dexamethasone prevents some structural changes in the pulmonary arteries of surgically created diaphragmatic hernia in rabbits

PURPOSE: Characterization of the structural changes occurring in the pulmonary arteries resulting from surgically produced congenital diaphragmatic hernia in rabbits, with particular emphasis on the preventive effects of prenatal tracheal ligation or administration of intra-amniotic dexamethasone or surfactant. METHODS: Twenty rabbit fetuses underwent surgical creation of a left-sided congenital diaphragmatic hernia on the 24th or 25th gestational day. They were divided according to the following procedures: congenital diaphragmatic hernia (n = 5), congenital diaphragmatic hernia plus tracheal ligation (n = 5), congenital diaphragmatic hernia plus intra-amniotic administration of dexamethasone 0.4 mg (n = 5) or surfactant (Curosurf 40 mg, n = 5). On gestational day 30, all the fetuses were delivered by caesarean section and killed. A control group consisted of five nonoperated fetuses. Histomorphometric analysis of medial thickness, cell nuclei density, and elastic fiber density of pulmonary arterial walls was performed. RESULTS: Arteries with an external diameter > 100 mum have a decreased medial thickness, lower cell nuclei density, and greater elastic fiber density when compared with arteries with external diameter <= 100 mum. Congenital diaphragmatic hernia promoted a significant decrease in medial thickness and an increase in cell nuclei density in artery walls with external diameter > 100 mum. Prenatal treatments with tracheal ligation or intra-amniotic administration of dexamethasone or surfactant prevented these changes. In arteries with external diameter <= 100 mum, congenital diaphragmatic hernia promoted a significant increase in medial thickness and in cell nuclei density and a decrease in elastic fiber density. The prenatal treatments with tracheal ligation or intra-amniotic administration of dexamethasone or surfactant prevented these changes, although no effect was observed in elastic fiber density in the congenital diaphragmatic hernia plus dexamethasone group. CONCLUSIONS: Congenital diaphragmatic hernia promoted different structural changes for large or small arteries. The prenatal intra-amniotic administration of dexamethasone or surfactant had positive effects on the lung structural changes promoted by congenital diaphragmatic hernia, and these effects were comparable to the changes induced by tracheal ligation.

Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema

OBJECTIVE: To compare the effects of 3 types of noninvasive respiratory support systems in the treatment of acute pulmonary edema: oxygen therapy (O2), continuous positive airway pressure, and bilevel positive pressure ventilation. METHODS: We studied prospectively 26 patients with acute pulmonary edema, who were randomized into 1 of 3 types of respiratory support groups. Age was 69±7 years. Ten patients were treated with oxygen, 9 with continuous positive airway pressure, and 7 with noninvasive bilevel positive pressure ventilation. All patients received medicamentous therapy according to the Advanced Cardiac Life Support protocol. Our primary aim was to assess the need for orotracheal intubation. We also assessed the following: heart and respiration rates, blood pressure, PaO2, PaCO2, and pH at begining, and at 10 and 60 minutes after starting the protocol. RESULTS: At 10 minutes, the patients in the bilevel positive pressure ventilation group had the highest PaO2 and the lowest respiration rates; the patients in the O2 group had the highest PaCO2 and the lowest pH (p<0.05). Four patients in the O2 group, 3 patients in the continuous positive pressure group, and none in the bilevel positive pressure ventilation group were intubated (p<0.05). CONCLUSION: Noninvasive bilevel positive pressure ventilation was effective in the treatment of acute cardiogenic pulmonary edema, accelerated the recovery of vital signs and blood gas data, and avoided intubation.

Role of eosinophilic airway inflammation in models of asthma

Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR) to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.

Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

Collection of tracheal aspirate: safety and microbiological concordance between two techniques

Objective: To evaluate the safety of the performance of the traditional and protected collection techniques of tracheal aspirate and to identify qualitative and quantitative agreement of the results of microbiological cultures between the techniques. Method: Clinical, prospective, comparative, single-blind research. The sample was composed of 54 patients of >18 years of age, undergoing invasive mechanical ventilation for a period of ≥48 hours and with suspected Ventilator Associated Pneumonia. The two techniques were implemented in the same patient, one immediately after the other, with an order of random execution, according to randomization by specialized software. Results: No significant events occurred oxygen desaturation, hemodynamic instability or tracheobronchial hemorrhage (p<0.05) and, although there were differences in some strains, there was qualitative and quantitative agreement between the techniques (p<0.001). Conclusion: Utilization of the protected technique provided no advantage over the traditional and execution of both techniques was safe for the patient.


Patient safety and the prevention of skin and mucosal lesions associated with airway invasive devices

AbstractOBJECTIVETo analyze the care implemented by the nursing team to promote the safety of adult patients and prevention of skin and mucosal lesions associated with the presence of lower airways invasive devices.METHODStudy with qualitative and quantitative approach, descriptive and exploratory type, whose investigative scenarios were adult inpatient units of a hospital in the West Frontier of Rio Grande do Sul. The study subjects consisted of nurses, nursing technicians and nursing assistants.RESULTSA total of 118 professionals were interviewed. We highlight the observed specific care with endotracheal tube and tracheostomy, management and assessment of the cuff and the criteria used to secretion aspiration.CONCLUSIONThere is a superficial nursing work in the patient direct care and a differentiation in relation to the perception of nurse technicians, especially those working in the intensive care unit, who presented major property and view of the patient's clinical status.

Tratamento cirúrgico do schwannoma traqueal

Schwannoma is a rare benign tumor of the proximal tracheobronchial tree. The aim of the present study is to report a case of tracheal schwannoma causing airway obstruction. A 16-year-old woman complained of cough, wheezing and dyspneia. Bronchoscopy and computerized tomography showed a polypoide intratracheal mass obstructing approximately 80% of the lumen. The treatment consisted of tracheal resection and primary anastomosis. Histological analysis revealed a tracheal schwannoma. The postoperative course was uneventful and the patient remains well twelve months after surgery.

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

Transitory increased blood pressure after upper airway surgery for snoring and sleep apnea correlates with the apnea-hypopnea respiratory disturbance index

A transitory increase in blood pressure (BP) is observed following upper airway surgery for obstructive sleep apnea syndrome but the mechanisms implicated are not yet well understood. The objective of the present study was to evaluate changes in BP and heart rate (HR) and putative factors after uvulopalatopharyngoplasty and septoplasty in normotensive snorers. Patients (N = 10) were instrumented for 24-h ambulatory BP monitoring, nocturnal respiratory monitoring and urinary catecholamine level evaluation one day before surgery and on the day of surgery. The influence of postsurgery pain was prevented by analgesic therapy as confirmed using a visual analog scale of pain. Compared with preoperative values, there was a significant (P < 0.05) increase in nighttime but not daytime systolic BP (119 ± 5 vs 107 ± 3 mmHg), diastolic BP (72 ± 4 vs 67 ± 2 mmHg), HR (67 ± 4 vs 57 ± 2 bpm), respiratory disturbance index (RDI) characterized by apnea-hypopnea (30 ± 10 vs 13 ± 4 events/h of sleep) and norepinephrine levels (22.0 ± 4.7 vs 11.0 ± 1.3 µg l-1 12 h-1) after surgery. A positive correlation was found between individual variations of BP and individual variations of RDI (r = 0.81, P < 0.01) but not between BP or RDI and catecholamines. The visual analog scale of pain showed similar stress levels on the day before and after surgery (6.0 ± 0.8 vs 5.0 ± 0.9 cm, respectively). These data strongly suggest that the cardiovascular changes observed in patients who underwent uvulopalatopharyngoplasty and septoplasty were due to the increased postoperative RDI.

Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection

An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 ± 0.43, P <= 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens.