Smoking induces increased apoptosis in osteoblasts: changes in bone matrix organic components.

Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses "in situ" using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1ß, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.

Aerobic exercise training engages cholinergic signaling to improve emphysema induced by cigarette smoke exposure in mice.

Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown. AIMS: As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema. MAIN METHODS: Wild-type (WT) and mutant (KDHOM) mice (65-70% of reduction in VAChT levels) were exposed to cigarette smoke (30 min, 2×/day, 5×/week, 12 weeks) and submitted or not to aerobic exercise training on a treadmill (60 min/day, 5×/week, 12 weeks). Lung function and inflammation were evaluated. KEY FINDINGS: Cigarette smoke reduced body mass in mice (p < 0.001) and increased alveolar diameter (p < 0.001), inflammation (p < 0.001) and collagen deposition (p < 0.01) in lung tissue. Both trained groups improved their performance in the final physical test compared to the initial test (p < 0.001). In WT mice, exercise training protected against emphysema development (p < 0.05), reduced mononuclear cells infiltrate (p < 0.001) and increased MAC-2 positive cells in lung parenchyma (p < 0.05); however, these effects were not observed in KDHOM mice. The exercise training reduced iNOS-positive cells (p < 0.001) and collagen fibers deposition (p < 0.05) in lung parenchyma of WT and KDHOM mice, although KDHOM mice showed higher levels of iNOS-positive cells. SIGNIFICANCE: Our data suggest that the protective effects of aerobic exercise training on pulmonary emphysema are, at least in part, dependent on the integrity of the lung cholinergic signaling.

Exposure to Sodium Hypochlorite or Cigarette Smoke Induces Lung Injury and Mechanical Impairment in Wistar Rats.

Pulmonary irritants, such as cigarette smoke (CS) and sodium hypochlorite (NaClO), are associated to pulmonary diseases in cleaning workers. We examined whether their association affects lung mechanics and inflammation in Wistar rats. Exposure to these irritants alone induced alterations in the lung mechanics, inflammation, and remodeling. The CS increased airway cell infiltration, acid mucus production, MMP-12 expression, and alveolar enlargement. NaClO increased the number of eosinophils and macrophages in the bronchoalveolar lavage fluid, with cells expressing IL-13, MMP-12, MMP-9, TIMP-1, and iNOS in addition to increased IL-1ß and TNF-α levels. Co-exposure to both irritants increased epithelial and smooth muscle cell area, acid mucus production, and IL-13 expression in the airways, while it reduced the lung inflammation. In conclusion, the co-exposure of CS with NaClO reduced the pulmonary inflammation, but increased the acidity of mucus, which may protect lungs from more injury. A cross-resistance in people exposed to multiple lung irritants should also be considered.

Airway inflammatory profile among cleaning workers from different workplaces.

BACKGROUND: Cleaning workers represent a significant proportion of the active population worldwide, with poor remuneration, particularly in developing countries. Despite this, they remain a relatively poorly studied occupational group. They are constantly exposed to agents that can cause symptoms and respiratory problems. This study aimed to evaluate upper airway inflammation in professional cleaning workers in three different occupational settings by comparing nasal cytology inflammation and clinical profiles. METHODS: We performed a cross-sectional study on the prevalence of upper airway inflammation and symptoms of asthma/rhinitis related to cleaning work, according to workplace. A total of 167 participants were divided into four groups: hospital, university, housekeeper and control. A nasal swab was collected for upper airway inflammation evaluation. Clinical profiles and respiratory symptom employee evaluations were performed using specific questionnaires (European Community Respiratory Health Survey-ECRS and the International Study of Asthma and Allergies in Childhood-ISAAC). RESULTS: Cleaning workers showed increased neutrophils and lymphocytes; the hospital and university groups showed increased macrophages compared to the housekeeper and control groups. The hospital and housekeeper groups showed increased eosinophils when they performed cleaning services for up to one year and reported having more asthma symptoms than the control group. Cleaning workers showed increased rhinitis symptoms. The university group showed increased rhinitis symptoms aggravated by the workplace compared with the hospital and housekeeper groups. Cleaning workers showed an increased affirmative response when directly asked about rhinitis symptoms compared to the control group. CONCLUSIONS: Cleaning workers showed airway inflammation, asthma symptoms and rhinitis, regardless of the occupational environment to which they were exposed, as well as showed increased rhinitis and asthma symptoms. Hospital cleaning workers showed increased macrophages, lymphocytes and eosinophils compared to the others. The length of time spent performing cleaning work was not related to nasal inflammation or respiratory symptoms in this population. However, there were differences in workplaces. Registered on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT03311048. Registration date: 10.16.2017. Retrospectively registered.

Cold bubble humidification of low-flow oxygen does not prevent acute changes in inflammation and oxidative stress at nasal mucosa.

Some clinical situations require the use of oxygen therapy for a few hours without hypoxemia. However, there are no literature reports on the effects of acute oxygen therapy on the nasal mucosa. This study aimed to evaluate the acute effects of cold bubble humidification or dry oxygen on nasal Inflammation, oxidative stress, mucociliary clearance, and nasal symptoms. This is a randomized controlled cross-sectional study in which healthy subjects were randomly allocated into four groups: (1) CA + DRY (n = 8): individuals receiving dry compressed air; (2) OX + DRY (n = 8): individuals receiving dry oxygen therapy; (3) CA + HUMID (n = 7): individuals receiving cold bubbled humidified compressed air; (4) OX + HUMID (n = 8): individuals receiving cold bubbled humidified oxygen therapy. All groups received 3 L per minute (LPM) of the oxygen or compressed air for 1 h and were evaluated: total and differential cells in the nasal lavage fluid (NLF), exhaled nitric oxide (eNO), 8-iso-PGF2α levels, saccharin transit test, nasal symptoms, and humidity of nasal cannula and mucosa. Cold bubble humidification is not able to reduced nasal inflammation, eNO, oxidative stress, mucociliary clearance, and nasal mucosa moisture. However, subjects report improvement of nasal dryness symptoms (P < 0.05). In the conclusion, cold bubble humidification of low flow oxygen therapy via a nasal cannula did not produce any effect on the nasal mucosa and did not attenuate the oxidative stress caused by oxygen. However, it was able to improve nasal symptoms arising from the use of oxygen therapy.

Low-dose chlorine exposure impairs lung function, inflammation and oxidative stress in mice.

AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1ß, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1ß and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1ß, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1ß and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.

The effects of particulate matter on inflammation of respiratory system: Differences between male and female.

Air pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n=34) and females (n=111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied. Hyperreactivity increased in CAPs-exposed female mice compared with AA-exposed mice in estrus (p<0.05) and proestrus phases (p<0.05) and decreased in CAPs-exposed males compared with those exposed to AA (p<0.05). Males had increased numbers of total cells (p=0.037) and macrophages (p=0.028) compared to females. BALF levels of cyclooxygenase-2(COX-2) (p=0.000), transforming growth factor alpha (TGF-α) (p=0.001) and IL-8 receptor alpha (IL-8Rα) (p=0.014) were increased in males compared with proestrus, estrus and diestrus females, independent of exposure. Proestrus females exhibited significantly higher cadherin expression in lung parenchyma than did males (p=0.005). CAPs exposure increased matrix metalloproteinase-9 (MMP-9) (p=0.024) and isoprostane (p=0.003) expression in the airways of both, males and females. The level of substance P (SP) (p=0.001) increased in lung parenchyma in males compared with females, while IL-17 levels in airways (p=0.042) and in lung parenchyma (p=0.008) increased in females. MMP-9 levels (p=0.024) were significantly lower in the lung parenchyma of CAPs-exposed females. TGF-α (p=0.007) levels increased in the lung parenchyma of CAPs-exposed females compared to AA-exposed females. These results suggest that inflammatory markers differentially expressed in male mice were mostly linked to acute inflammation (IL-1ß, IL-8Rα, COX-2), whereas in females, markers that may lead to a chronic inflammatory process such as IL-17 and remodeling (MMP-9) were increased.

Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation.

BACKGROUND AND PURPOSE: Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma. METHODS: Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30days and were treated with or without sakuranetin (20mg/kg/mice) or dexamethasone (5mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels. RESULTS: We demonstrated that sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of sakuranetin was similar to the dexamethasone effect. CONCLUSIONS AND IMPLICATIONS: Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.