Early Stages Of Asthma Research Articles

Sharbat Zoofa Murakkab, A Promising Unani Formulation for Sual (Cough)

It has been described that Sual (cough) is the movement of lungs to remove or reduce the painful stress on the lungs). Cough is a physiologically useful protective reflex that clears the respiratory tract. It occurs due to stimulation of chemo receptors in throat, respiratory passages or stretch receptors in the lungs. According to Unani scholars, Sual (cough) is an act by which Tabiyat removes Aziyat (irritating substances) from the lungs, cough with mucus and sputum. It affects mainly quality of life, works productivity and public health resources etc. The drugs available in the modern medicine produce more or less side effects in the human body. The Unani classical formulation is traditionally used for the treatment of cough, early stages of asthma and useful in bronchial Asthma, phlegmatic cough. Expel phlegm from the chest. It is used to clear mucus from the chest and clear chest congestion. It is 100% natural and vegetarian product. No side effects of Sharbat Zoofa Murakkab mentioned and reported in Unani classical literature and a clinical study was conducted by the Central Council for Research in Unani Medicine under Ministry of AYUSH, Government of India, more studies are required to validate the Pharmacopeial formulation on large scale.

Ubi-Asthma: Toward Ubiquitous Asthma Detection Using the Smartwatch

Asthma is a common respiratory disease in modern society. However, people are rarely aware of the symptoms of asthma because the early stage of asthma is similar to that of the common cold (e.g., wheeze, cough, shortness of breath). To tackle this challenge, we propose an asthma detection system, Ubi-Asthma, based on the smartwatch. Ubi-Asthma combines breathing signals and guttural sound (e.g., cough sound and throat-clearing sound) signals to realize passive and accurate asthma detection without interrupting the user. Not only can Ubi-Asthma extract breathing signals from the user even if the user is walking, but also recognize guttural sound signals when the user is engaged in voice communication without being disturbed by noise. The features of breathing and guttural sound are combined to improve the accuracy of asthma detection. We have implemented a fully functional prototype using an off-the-shelf smartwatch. Fifty volunteers participate in an extensive experiment of up to 150 hours to train Ubi-Asthma. As a result, Ubi-Asthma can reach a detection accuracy of 98.4%, which is higher than breath-or guttural-based asthma detection systems. Ubi-Asthma is expected to provide a potential solution for smart-home applications in the future.

Eosinophilic bronchitis: update and review

Eosinophilic bronchitis (EB) is a common cause of chronic cough, which shares similar airway eosinophilic inflammation with asthma, however, there is no airway hyperresponsiveness and airflow obstruction. The mechanism of the different phenotype between EB and asthma remains unclear. The differences in the location of airway inflammation, the level of inflammatory mediators, the imbalance of important metabolic pathways, and the degree of airway remodeling may result in different pathogenesis between EB and asthma. EB response well to inhaled corticosteroids but recurrence of EB is still high after treatment. The longer duration of treatment with inhaled corticosteroids could decrease the relapse rate. On the prognosis of EB, a long-term follow-up study suggested that EB should be a distinct entity rather than an early stage of asthma or chronic obstructive pulmonary disease.

α-Asarone alleviates allergic asthma by stabilizing mast cells through inhibition of ERK/JAK2-STAT3 pathway.

Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α-Asarone is an important anti-inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α-asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α-asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell-dependent asthma model. Western blot was performed to determine the underlying pathway. α-Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL-8, MCP-1, histamine, and TNF-α in vitro. α-Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF-α in vivo. In the asthma model, α-asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL-5 and IL-13 in lung tissue. α-Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α-asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2-STAT3 pathway.

The place of impulse oscillometry system in the diagnosis of early obstructive disorders associated with asthma

Asthma is one of the most common and socially significant human diseases. To date, spirometry is included in most recommendations as the gold standard for the diagnosis of obstructive disorders. However, in real clinical practice, this procedure does not always reveal signs of bronchial obstruction, not only in the early stages of the disease but also in more severe controlled bronchial asthma. Tests of oscillatory mechanics are increasingly being used to detect early violations of the pulmonary ventilation function. These tests are based on the forced oscillation technique, and the latest modification is impulse oscillometry system. Theaimof this study was to investigate the capabilities of impulse oscillometry in diagnosing early changes in the function of the respiratory system in patients with asthma and identifying the most informative parameters of the method.Methods. A total of 146 patients with an established diagnosis of mild and moderate asthma were examined during remission. The patients were divided into 2 groups by the severity of asthma. The comparison group included 40 people with no signs of lung abnormalities.Results. Disorders of the pulmonary ventilation function were found in 23% of patients with asthma by spirometry, in 42% by bodypletismography in 42%, and in 72% of patients by impulse oscillometry. Impulse oscillometry system revealed obstructive changes localized in the central respiratory tract in 11% of patients, and obstruction of mixed localization was found in 6% of respondents. Peripheral respiratory tract disorders were diagnosed in 56 % of patients. Most respiratory tract lesions were located in the small bronchi in both groups. The obstructive disorders in large bronchi and generalized obstruction were observed more often in the 2ndgroup. Among impulse oscillometry parameters, the increase in Delta (Rrs5– Rrs20) was most often recorded in both examined groups of patients with asthma.Conclusion. Compared to standard methods, impulse oscillometry system is more sensitive. Therefore, it has advantages in diagnosing respiratory system dysfunctions both in the early stages of asthma and in more severe cases during remission.

Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma.

Background:Cough variant asthma (CVA), a suggested precursor of standard bronchial asthma (SBA), is characterized by positive bronchial hyperresponsiveness (BHR) and a chronic cough response to bronchodilator that persists for >8 weeks.Objective:Airway inflammation, BHR, and airway obstructive damage were analyzed to assess whether CVA represents early or mild-stage SBA.Methods:Patients with newly diagnosed CVA (n = 72) and SBA (n = 84) naive to oral or inhaled corticosteroids and without exacerbated asthma were subjected to spirometry, impulse oscillometry, BHR tests, sputum induction, and fractional exhaled nitric oxide measurements.Results:In the patients with CVA, spirometry demonstrated higher forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio, FEV1 percent predicted, flow volume at 50% of vital capacity % predicted, and flow volume at 25% of vital capacity % predicted values, and impulse oscillometry demonstrated lower R5–Z20, AX, and Fres, and higher X5 values. In addition, the fractional exhaled nitric oxide and sputum eosinophil numbers were lower and the PC20 was higher than in patients with moderate SBA. However, these factors were similar in the patients with CVA and in the patients with intermittent mild SBA. A significantly smaller proportion of the patients with CVA had increased sputum eosinophils than the patients with intermittent mild SBA (p < 0.0001). However, interestingly, among the patients with CVA, no significant differences in the PC20 values were found between the patients with and those without increased sputum eosinophils.Conclusions:All measures of central and peripheral airway obstruction, eosinophilic inflammation, and airway hyperresponsiveness in patients with CVA were milder than in patients with moderate SBA but were similar to those of patients with intermittent mild SBA. In CVA, the BHR was not affected by airway eosinophilic inflammation, which indicated that the very early development of BHR may not always need airway eosinophilic inflammation.

Increased epidermal growth factor in nasopharyngeal aspirates from infants with recurrent wheeze.

Airway remodeling is known to be a consequence of repeated injury and thought to be involved in early stage of asthma. We aimed to investigate the mediators associated with airway remodeling in recurrent early wheezers. Thirty-three infants, aged 2 years or less, admitted with exacerbation of wheezing were enrolled. All of them had experienced three or more episodes of wheezing before admission. They were categorized into two groups: those who had been hospitalized two or more times for severe wheezing (N = 19) and those who had only once or never been hospitalized (N = 14). Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1 levels in nasopharyngeal aspirates (NPA) collected on admission were measured. The difference between two patients groups divided based on their hospitalization history was assessed. We also examined these mediators in older asthmatic children (N = 15) admitted with exacerbation and their relationship with lung function parameters measured after stabilization. NPA EGF levels were significantly increased in recurrent early wheezers compared to controls. EGF, VEGF, and TGF-β1 levels were significantly higher in those with a previous history of multiple hospitalizations than in those without. In older asthmatic children, EGF levels were related with age and duration of asthma, but showed an inverse correlation with forced expiratory volume in 1 sec and forced expiratory flow between 25% and 75% of vital capacity. Our study shows that there might be significant damage during exacerbation in wheezy infants as levels of the mediators, EGF, VEGF, and TGF-β1 were higher in those who had been frequently hospitalized. It seems to suggest that those infants with severe recurrent wheezing might have chronic airway obstruction.

When Should a Reversibility Test Be Performed on Patients with Early Stages of Asthma and Normal Spirometry?

Subjects with bronchial asthmatic symptoms, forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity [FVC] > 80% could show a positive reversibility test with salbutamol in about 25% of the cases. The aim of this study was to evaluate if a limit functional value for spirometry exists where a reversibility test using salbutamol, over this limit, is not necessary to confirm the diagnosis of asthma. Four hundred patients (mean age 31.12 ± 10.99) with asthmatic symptoms and normal spirometry (mean FEV1 96.06 ± 11.82%, mean FEV1/FVC 98.89 ± 6.03%) were recruited. The number of subjects with reversible airflow obstruction (RAO) was evaluated using the following different criteria of reversibility: FEV1 and FVC ≥ slant 12%, peak expiratory flow (PEF) ≥ slant 15%, FEF25 −75 ≥ slant 35%, and at least one of these (ANY). In subjects with baseline FEV1 > 100% (150 patients), 26 (17.3%) patients showed a FEV1 increase > 12% and, among the criteria used, 45 patients (30%) showed ANY. In subjects with baseline FEV1/FVC > 100% (204 patients), 36 patients (17.6%) showed a FEV1 increase > 12% and 53 patients (26.8%) showed ANY. In subjects with baseline FEF25 −75 > 70% (209 patients), 26 (12.44%) and 49 (23.44%) patients, respectively, showed an increase in FEV1 > 12%, and ANY. In 56 patients with baseline cut-offs (evaluated together) FEV1 > 100%, FEV1/FVC > 100% and FEF25−75 > 70%, 10 patients (17.85%) showed a RAO with ANY. FEV1 > 121% or FEV1/FVC > 110.8% or FEF25 −75 > 110% were cut-off values identified in this study where no RAO subjects were found over these limits. In conclusion, baseline FEV1 > 100%, FEV1/FVC > 100% and FEF25 −75 > 70% cannot be considered cut-offs where it is not necessary to perform a reversibility test with a bronchodilator over these limits. It is improbable to find a positive reversibility test using salbutamol in patients with asthmatic symptoms and FEV1 > 121% or FEV1/FVC > 110.8% or FEF25 −75 > 110% to confirm the diagnosis of asthma.

Chemokine Receptor 2 Blockade Prevents Asthma in a Cynomolgus Monkey Model

The pathophysiology of asthma is characterized by accumulation and activation of several cell types in the lung, which correlates with coordinated production of specific cytokines and chemokines. To study the effect of selective CCR2 chemokine receptor blockade on leukocyte recruitment to the lung and on bronchial function, we used a nonhuman primate model of allergic airway disease that closely resembles human asthma. Allergic cynomolgus monkeys were treated with the antagonist anti-CCR2 (CCR2-05) monoclonal antibody and then challenged with Ascaris suum antigen; the effect of antibody treatment on macrophage and eosinophil infiltration was determined. Pulmonary function was calculated by measurement of lung resistance and dynamic compliance. Local inflammatory responses were analyzed after intradermal challenge with A. suum antigen. CCL2 up-regulation in bronchoalveolar lavage (BAL) was analyzed by enzyme-linked immunosorbent assay, and in vitro CCR2-05 antagonistic activity was tested in monkey peripheral blood mononuclear cells using chemotaxis and calcium mobilization assays. The results show that neutralization of CCR2 reduces antigen-induced bronchial hyper-responsiveness and attenuates macrophage and eosinophil accumulation in the BAL of asthmatic monkeys. The results confirm that selective blockade of a single chemokine receptor involved in early stages of asthma can condition later disease stages and suggest the utility of anti-CCR2-neutralizing monoclonal antibodies in the treatment of asthma in man.

Growth Factors Temporally Associate with Airway Responsiveness and Inflammation in Allergen-Exposed Mice

Background: To clarify whether growth factors play critical roles in the development of airway hyperresponsiveness (AHR) and airway inflammation in the early stages of asthma, the relationship between growth factors and AHR and airway inflammation were analyzed in a mouse model of asthma. Methods: Following ovalbumin (OVA) sensitization and challenge, airway function, inflammation, cytokine and growth factor levels were monitored. Results: AHR to inhaled methacholine increased at 6 h, peaked at 48 h, and remained elevated for 14 days. IL-4 and IL-5 levels in bronchoalveolar lavage (BAL) fluid were increased at 6 h, peaked at 24 h, but returned to baseline quickly. IL-13 levels increased up to 14 days, peaking at 48 h. Increases in BAL fluid transforming growth factor-β₁ and platelet-derived growth factor were observed at 12 h, and remained elevated at 14 days. Nerve growth factor levels were increased at 24–28 days. BAL fluid hepatocyte growth factor (HGF) was detected at 12 h, peaked at 24 h, and returned to baseline by 72 h. c-Met/HGF receptor was detected in the airways at 6 h, before HGF in the BAL, and continued to be observed 96 h after the last OVA challenge. Conclusions: These data identify a temporal association between growth factor production and Th2 cytokine production and the kinetics of AHR. Growth factors may play important roles in the development of allergic airway inflammation and AHR even in the early stages of asthma, before remodeling is initiated.

Update in asthma management

Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called ‘airway remodeling’ and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.

Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma.

The type 2 helper T cell (T(H)2) cytokine interleukin (IL)-4 is thought to play a central role in the early stages of asthma. In an effort to develop an antibody treatment for asthma that neutralizes the effects of IL-4, a murine monoclonal antibody, 3B9, was generated with specificity for human IL-4. In vitro studies demonstrated that 3B9 inhibited IL-4-dependent events including IL-5 synthesis, (T(H)2) cell activation and up-regulation of immunoglobulin E expression. 3B9 was then humanized (pascolizumab, SB 240683) to reduce immunogenicity in humans. SB 240683 demonstrated species specificity for both monkey and human IL-4 with no reactivity to mouse, rat, cow, goat or horse IL-4. Pascolizumab inhibited the response of human and monkey T cells to monkey IL-4 and effectively neutralized IL-4 bioactivity when tested against several IL-4-responsive human cell lines. Affinity studies demonstrated rapid IL-4 binding by pascolizumab with a slow dissociation rate. In vivo pharmacokinetic and chronic safety testing in cynomolgus monkeys demonstrated that pascolizumab was well tolerated, and no adverse clinical responses occurred after up to 9 months of treatment. Three monkeys developed an anti-idiotypic response that resulted in rapid pascolizumab clearance. However, in the chronic dosing study the antibody response was transient and not associated with clinical events. In conclusion, pascolizumab is a humanized anti-IL-4 monoclonal antibody that can inhibit upstream and downstream events associated with asthma, including (T(H)2) cell activation and immunoglobulin E production. Clinical trials are under way to test the clinical efficacy of pascolizumab for asthma.

Effects of Tachykinins and Histamine on the Expression of Thymus- and Activation-Regulated Chemokine mRNA in Peripheral Blood Mononuclear Cells and Human Bronchial Epithelial Cells.

We hypothesized that participation of sensory neuropeptides, substance P and neurokinin A in the airway inflammation caused to resistance against the glucocorticoids (GCs) treatment. We have measured the expression level of cytokines and chemokines mRNAs in bronchoalveolar lavage cells (BAL), transbronchial lung biopsies (TBLB) and peripheral blood mononuclear cells (PBMC) by reverse transcriptase polymerase chain reaction (RTPCR). The mRNAs of interleukin-4 (IL-4) and -5, which are typical Thelper 2 (Th2)-type cytokines, were scarcely detected in all of bronchoalvelar lavage fluid (BALF) and TBLB samples. But the mRNA of Th1-type cytokines, such as IL-12, IL-18, and interferon-γ (IFN-γ), tended to be expressed higher than that of Th2-type cytokines at the early stage of asthma before intervention with GCs. The mRNAs of IL-18, IFN-γ, macrophage-derived chemokine (MDC) and thymus- and activation-regulated chemokine (TARC) tended to be expressed higher than that of nonasthmatic subjects. In vitro study demonstrated that the expression of TARC mRNA induced by the combination of IL-4, IFN-γ, and neurokinin A in human bronchial epithelial cells, BEAS-2B was not inhibited by the treatment of the cells with dexamethasone even at 10 ‐6 M. We proposed that the part of resistance to GCs in the asthmatic patient without GC receptor β expression might be associated with the induction of TARC expression in airway epithelial cells by tachykinines and histamine.

Compliance During Long-Term Treatment with Fluticasone Propionate in Subjects with Early Signs of Asthma or Chronic Obstructive Pulmonary Disease (COPD): Results of the Detection, Intervention, and Monitoring Program of COPD and Asthma (DIMCA) Study

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk®) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with “early signs of COPD” (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with “early signs of asthma” (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide® 500 jag daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

The long-term influence of therapeutic interventions in asthma with emphasis on inhaled steroids and early disease.

The data available to show the long-term benefits of any pharmacological interventions in asthma is scanty. Usually the beneficial effects disappear gradually when the treatment is withdrawn. The evidence showing that treatment with drugs could change the natural course of asthma is largely lacking. Only a few controlled studies have lasted more than 1 year, while asthma can be a disease for life. Nevertheless, the short-term benefits of treatment with inhaled steroids justify their introduction as soon as the diagnosis of asthma is established. Regular use of inhaled steroids especially during the early stages of asthma often makes it a less troublesome disease. Regular use of long-acting beta2-agonists is useful in preventing exacerbations in persistent asthma, but their influence on the long-term outcome is quite unknown. Exploration of the possible disease outcome modifying effect of new innovations such as leukotriene antagonists should be put in the clinical study programmes. In future, the combination of immunological and pharmacological treatments may offer the key for more permanent results in asthma therapy.

The Relationship Between Psychosocial Aspects and Aggravation of Childhood Asthma

The relationship between psychosocial aspects of asthmatic children and aggravation of asthma was investigated. Five studies investigated (1) the acquisition of basic trust and initiative development; (2) the psychological factors of asthma; (3) personality traits; (4) basic habits of life; and (5) problem behaviors. The more severe their asthma and the older patients became, the more psychosocial disturbances tended to appear. It can be tentatively concluded that psychosocial disturbances were secondarily caused by recurrent asthma; the disturbances, in turn, promoted aggravation of the patients' asthma. The results suggest that asthmatic children should be comprehensively treated in the early stages of asthma.

The relationship between age and duration of asthma and the presence of persistent obstruction in asthma.

Persistent obstruction was assessed in 630 asthmatic subjects by measurement after bronchodilator of the maximum potential peak flow rate and forced vital capacity. Persistent obstruction was directly related to duration of asthma. The fit was slightly better after logarithmic transformation, suggesting that the early stages of asthma may be as important as the later ones in the development of persistent obstruction. On multivariate analysis age was an additional factor in males, but made no significant difference to females. Atopy did not prove relevant. Measurements of peak flow suggested a more rapid deterioration in males of social classes III, IV and V than classes I and II. Although current smokers had lower peak flow rate and vital capacity than non-smokers, there was no evidence of a steeper decline in smokers than non-smokers suggesting that the effect of cigarette smoking was at most additive to that of duration of asthma.