In view of the tragic fire at a nightclub in the city of Santa Maria, Brazil, which culminated in the sudden death of 232 young people, we decided to review the literature regarding smoke inhalation injury caused by enclosed-space fires, which can be divided into direct thermal damage, carbon monoxide poisoning, and cyanide poisoning. Such injuries often call for immediate orotracheal intubation, either due to acute airway obstruction or due to a reduced level of consciousness. The diagnosis and the severity of the thermal injury can be determined by fiberoptic bronchoscopy. The levels of gases and gas by-products in the bloodstream should be assessed as rapidly as possible, even while still at the scene of the incident. First responders can also treat carbon monoxide poisoning, with immediate administration of oxygen at 100%, as well as cyanide poisoning, with oxygen therapy and hydroxocobalamin injection.

Keywords: Smoke inhalation injury; Carbon monoxide; Cyanides.

Inhalation injury is the main cause of death in burn patients and has therefore, understandably, been the subject of numerous published studies. The pathogenesis of inhalation injury involves both local and systemic mechanisms, thereby increasing the repercussions of the injury. The search for tools that would allow earlier diagnosis of inhalation injury and for treatment strategies to lessen its deleterious effects is ongoing. In this review, we describe the physiopathological mechanisms of inhalation injury, as well as the current diagnostic tools and treatment strategies used in patients suffering from inhalation injury. We also attempt to put experimental therapeutic approaches into perspective.

Keywords: Smoke inhalation injury/diagnosis. Smoke inhalation injury/pathophysiology. Smoke inhalation injury/ complications. Burns, inhalation/therapy. Review literature. Carbon monoxide. Poisoning/complications.

Objective: To analyze bronchoalveolar lavage (BAL) specimens of burn victims who inhaled smoke, in order to identify alterations associated with mortality or survival. Methods: Eighteen victims of facial burns were submitted to BAL up to 24 h after the event. We investigated cell and protein content, including TNF-α, HLA-DR, CD14, CD68 and iNOS. Results: Of the 18 patients submitted to bronchoscopy, 8 (44.4%) died during the follow-up period. The mean age of patients who died was significantly higher (44.7 vs. 31.5 years). On average, the patients who died had burns covering 60.1% of the total body surface area, compared with 26.1% in the survivors (p < 0.0001). Of the 18 patients submitted to bronchoscopy, 11 (61.1%) showed endoscopic signs of smoke inhalation injury, and 4 (36.4%) of those 11 died. Of the 7 patients with no signs of smoke inhalation injury, 4 (57.1%) died. The mean number of ciliated epithelial cells in the BAL fluid was significantly higher in the patients who died than in the survivors (6.6% vs. 1.4%; p = 0.03). There were no significant differences between the groups in terms of any of the other parameters evaluated. Conclusions: The total body surface area burned was a predictive factor for mortality. Increased numbers of ciliated epithelial cells in the BAL fluid, denoting bronchial epithelial desquamation, were associated with higher mortality in patients with facial burns.

Keywords: Burns; Smoke inhalation injury; Bronchoalveolar lavage; Epithelial cells; Macrophages;Tumor necrosis factor-alpha.

Objective: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. Methods: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). Results: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. Conclusions: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity.

Keywords: Inflammation; Inhalation exposure; Tobacco smoke pollution.

Objetivo: Investigar os efeitos agudos da administração endovenosa de extrato da fumaça do cigarro (EFC) em parâmetros funcionais respiratórios, inflamatórios e histológicos em ratos e comparar esse potencial modelo de lesão pulmonar aguda (LPA) com aquele com o uso de ácido oleico (AO). Métodos: Foram estudados 72 ratos Wistar machos divididos em quatro grupos: tratados somente com soro fisiológico (SF; grupo controle); tratados com EFC e SF (grupo EFC); tratados com SF e AO (grupo AO); e tratados com EFC e AO (grupo EFC/AO). Resultados: As médias de complacência foram significantemente menores nos grupos AO e EFC/AO (2,12 ± 1,13 mL/cmH2O e 1,82 ± 0,77 mL/cmH2O, respectivamente) do que no controle (3,67 ± 1,38 mL/cmH2O). A proporção de neutrófilos e a atividade das metaloproteinases 2 e 9 em lavado broncoalveolar foram significantemente maiores nos grupos AO e EFC/AO que no controle. O acometimento pulmonar avaliado por morfometria foi significantemente maior nos grupos AO e EFC/AO (72,9 ± 13,8% e 77,6 ± 18,0%, respectivamente) do que nos grupos controle e EFC (8,7 ± 4,1% e 32,7 ± 13,1%, respectivamente), e esse acometimento foi significantemente maior no grupo EFC que no grupo controle. Conclusões: A administração endovenosa de EFC, nas doses e tempos deste estudo, associou-se à LPA mínima. O EFC não potencializou a LPA induzida por AO. Estudos adicionais são necessários para esclarecer o papel potencial desse modelo como método de estudo dos mecanismos de agressão pulmonar pelo tabaco.

Keywords: Tabagismo; Lesão pulmonar aguda; Modelos animais.

Objetivo: Avaliar o dano oxidativo (oxidação lipídica, oxidação proteica, thiobarbituric acid-reactive substances [TBARS, substâncias reativas ao ácido tiobarbitúrico], e carbonilação) e inflamação (expressão de phosphorylated AMP-activated protein kinase e de phosphorylated mammalian target of rapamycin (p-AMPK e p-mTOR, respectivamente) em tecido pulmonar e músculos do diafragma em camundongos C57BL/6 machos expostos à fumaça de cigarro (FC) por 7, 15, 30, 45 ou 60 dias. Métodos: Trinta e seis camundongos machos da espécie C57BL/6 foram divididos em seis grupos (n = 6/grupo): grupo controle e 5 grupos expostos a FC por 7, 15, 30, 45 e 60 dias, respectivamente. Resultados: Comparados aos camundongos controle, os camundongos expostos à FC apresentaram menor peso corporal em 30 dias. Nos camundongos expostos à FC (comparados aos controle) as maiores diferenças (aumentos) nos níveis de TBARS foram observados no dia 7 no músculo diafragma, comparado ao dia 45 em tecido pulmonar; as maiores diferenças (aumentos) nos níveis de carbonilas foram observados no dia 7 em ambos os tipos de tecido; e os níveis de sulfidrilas foram menores, nos dois tipos de tecidos, em todos os tempos. No tecido pulmonar e no músculo diafragma, a expressão de p-AMPK exibiu um comportamento semelhante ao dos níveis de TBARS. A expressão de p-mTOR foi maior que o valor controle nos dias 7 e 15 no tecido pulmonar, assim como no dia 45 no músculo diafragma. Conclusões: Nossos dados demonstram que a exposição à FC produz dano oxidativo tanto no tecido pulmonar quanto (primariamente) no tecido muscular, tendo um efeito adicional no músculo respiratório, como é frequentemente observado em fumantes com DPOC.

Keywords: Oxidative stress; Mice; Respiratory system; Smoking; Inflammation.

Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients.

Keywords: Bronchial hyperreactivity; Drug delivery systems; Respiration, artificial.

The ischemia-reperfusion injury is a common pathophysiologic phenomenon in many diseases seen in daily clinical practice. The lung can be affected both directly, as in pulmonary edema after lung transplant or after resolution of pulmonary thromboembolism, and indirectly, as in shock states or after reperfusion injury in distant organs as intestine or lower extremities. The latter situation can occur secondary to aortic occlusion for surgical procedures. Many mediators have been implicated in the ischemia-reperfusion injury: oxygen free radicals, lipid products as thromboxane, adhesion molecules involved in leukocyte-endothelial interaction, tumor necrosis factor, among others. Therapeutic strategies for the reperfusion injury are used only at the experimental level and in very few clinical studies. Antioxidants, inhibitors of lipid mediators and of the leukocyte-endothelial interaction and promoters of blood flow in post-ischemic vessels have been used.

Keywords: Lung. Injury. Reperfusion. Ischemia.

Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related death in the United States and United Kingdom. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion. Although the mechanism of TRALI has not been fully elucidated, it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens) and with biologically active mediators in stored cellular blood components. Most of the donors implicated in cases of TRALI are multiparous women. Rarely diagnosed, TRALI can be confused with other causes of acute respiratory failure. Greater knowledge regarding TRALI on the part of clinicians could be crucial in preventing and treating this severe complication of blood transfusion.

Keywords: Blood transfusion; Respiratory insufficiency; HLA antigens.

Objective: To establish the incidence of acute lung injury and acute respiratory distress syndrome, as well as related risk factors and mortality in an intensive care unit. To compare patients developing lung injury with at-risk patients not presenting acute lung injury or acute respiratory distress syndrome. Methods: The study was conducted in the intensive care unit of the Ribeirão Preto Hospital das Clínicas Emergency Room. All patients admitted between May 2001 and April 2002 were monitored prospectively. Clinical data, Acute Physiologic and Chronic Health Evaluation II score, complications, length of stay in the intensive care unit and lung injury data were recorded. Results: Of the 524 patients admitted, 175 (33.4%) presented risk factors for acute lung injury and acute respiratory distress syndrome, 33 (6.3%) developed acute respiratory distress syndrome, and 12 (2.3%) developed acute lung injury. The main risk factors were pneumonia (37.7%), shock (32.0%), multiple trauma (24.6%) and sepsis (21.1%). Patients developing acute lung injury had higher Acute Physiologic and Chronic Health Evaluation II scores (p < 0.05), more frequently presented sepsis (p = 0.001), developed more complications (p = 0.001) and presented greater mortality (p = 0.001). The main cause of death was multiple organ failure (38.5%). Conclusion: The incidence of acute lung injury and acute respiratory distress syndrome was 2.3% and 6.3%, respectively.

Keywords: Respiratory distress syndrome, adult/epidemiology; Respiratory distress syndrome, adult/mortality;

Objective: To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE). Methods: A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days). At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region. Results: Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma. Conclusions: Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema.

Keywords: Tobacco; Models, animal; Emphysema; Respiratory physiological phenomena; Lung injury.

Objective: COPD is one of the major causes of morbidity and mortality worldwide. Health care providers should counsel their smoking patients with COPD to quit smoking as the first treatment step. However, in countries with high prevalences of smoking, health care workers may also be smokers. The aim of this study was to determine the frequency and severity of COPD in health care workers who smoke. Methods: This was a cross-sectional study. All health care workers who smoke, from nine health care centers in Serbia, were invited to participate in the study and perform spirometry. The diagnosis of COPD was based on a post-bronchodilator FEV1/FVC ratio of < 0.70. All patients completed the COPD Assessment Test and the Fagerström Test for Nicotine Dependence. Results: The study involved 305 subjects, and 47 (15.4%) were male. The mean age of the participants was 49.0 ± 6.5 years. Spirometry revealed obstructive ventilatory defect in 33 subjects (10.8%); restrictive ventilatory defect, in 5 (1.6%); and small airway disease, in 96 (31.5%). A diagnosis of COPD was made in 29 patients (9.5%), 25 (86.2%) of whom were newly diagnosed. On the basis of the Global Initiative for COPD guidelines, most COPD patients belonged to groups A or B (n = 14; 48.2%, for both); 1 belonged to group D (3.6%); and none, to group C. Very high nicotine dependence was more common in those with COPD than in those without it (20.7% vs. 5.4%, p = 0.01). Conclusions: In this sample of health care workers, the frequency of COPD was comparable with that in the general population. The presence of COPD in health care workers who smoke was associated with higher nicotine dependence.

Keywords: Pulmonary disease, chronic obstructive/prevention & control; Smoking; Health personnel.

Objective: To evaluate knowledge of and techniques for using prescribed inhalation devices among patients with asthma or COPD treated at a tertiary teaching hospital. Methods: Patients were assessed after medical visits, and their physicians were blinded to this fact. Patients were asked to demonstrate their inhaler technique and were then interviewed regarding their knowledge of inhalation devices, control of the disease and instructions received during medical visits. Results: We included 120 volunteers: 60 with asthma and 60 with COPD. All of the asthma patients and 98.3% of the COPD patients claimed to know how to use inhaled medications. In the sample as a whole, 113 patients (94.2%) committed at least one error when using the inhalation device. Patients committed more errors when using metered-dose inhalers than when using the dry-powder inhalers Aerolizer® (p < 0.001) or Pulvinal® (p < 0.001), as well as committing more errors when using the Aerolizer® inhaler than when using the Pulvinal® inhaler (p < 0.05). Using the metered-dose, Pulvinal® and Aerolizer® inhalers, the COPD group patients committed more errors than did the asthma group patients (p = 0.0023, p = 0.0065 and p = 0.012, respectively). Conclusions: Although the majority of the patients claimed to know how to use inhalation devices, the fact that 94.2% committed at least one error shows that their technique was inappropriate and reveals a discrepancy between understanding and practice. Therefore, it is not sufficient to ask patients whether they know how to use inhalation devices. Practical measures should be taken in order to minimize errors and optimize treatment.

Keywords: Metered dose inhalers; Nebulizers and vaporizers; Asthma; Pulmonary disease, chronic obstructive.

Objective: To validate two scores quantifying the ability of patients to use metered dose inhalers (MDIs) or dry powder inhalers (DPIs); to identify the most common errors made during their use; and to identify the patients in need of an educational program for the use of these devices. Methods: This study was conducted in three phases: validation of the reliability of the inhaler technique scores; validation of the contents of the two scores using a convenience sample; and testing for criterion validation and discriminant validation of these instruments in patients who met the inclusion criteria. Results: The convenience sample comprised 16 patients. Interobserver disagreement was found in 19% and 25% of the DPI and MDI scores, respectively. After expert analysis on the subject, the scores were modified and were applied in 72 patients. The most relevant difficulty encountered during the use of both types of devices was the maintenance of total lung capacity after a deep inhalation. The degree of correlation of the scores by observer was 0.97 (p < 0.0001). There was good interobserver agreement in the classification of patients as able/not able to use a DPI (50%/50% and 52%/58%; p < 0.01) and an MDI (49%/51% and 54%/46%; p < 0.05). Conclusions: The validated scores allow the identification and correction of inhaler technique errors during consultations and, as a result, improvement in the management of inhalation devices.

Keywords: Asthma; Dry powder inhalers; Metered dose inhalers; Validation studies.

Although mechanical ventilation is an important therapy, it can result in complications. One major complication is ventilator-induced lung injury, which is caused by alveolar hyperdistension, leading to an inflammatory process, with neutrophilic infiltration, hyaline membrane formation, fibrogenesis and impaired gas exchange. In this process, cellular mechanotransduction of the overstretching stimulus is mediated by means of the cytoskeleton and its cell-cell and cell-extracellular matrix interactions, in such a way that the mechanical stimulus of ventilation is translated into an intracellular biochemical signal, inducing endothelial activation, pulmonary vascular permeability, leukocyte chemotaxis, cytokine production and, possibly, distal organ failure. Clinical studies have shown the relationship between pulmonary distension and mortality in patients with ventilator-induced lung injury. However, although the cytoskeleton plays a fundamental role in the pathogenesis of ventilator-induced lung injury, there have been few in vivo studies of alterations in the cytoskeleton and in cytoskeleton-associated proteins during this pathological process.

Keywords: Respiration, artificial; Cytoskeleton; Cell adhesion molecules; Focal adhesions; Mechanotransduction, cellular