Ligustrazine Inhibits Lung Phosphodiesterase Activity in a Rat Model of Allergic Asthma

Objectives. This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. Methods. Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance ( R L ) and dynamic lung compliance ( C dyn ) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. Conclusions. Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.

Longitudinal Evaluation of Pulmonary Function in Premature Infants

Background: Infants born premature have decreased pulmonary function compared to full-term infants. Longitudinal infant studies are needed to determine whether impaired pulmonary function following premature birth demonstrates catch-up growth. This study measured airway and parenchymal function in infants born premature at approximately 6 months and 1 year of age to assess growth and the effects of gestational age (GA) and sex. Methods: 37 infants born premature participated in two study visits (V1 and V2) at Riley Hospital in Indianapolis, IN. While sleeping, forced expiratory maneuvers were preformed to measure airway function. DLCO, diffusion capacity of the lung, and VA, alveolar volume, were measured under conditions of room air. Z scores were calculated to compare infants born premature and full-term, adjusting for size, race, and sex. Demographics: The subjects consisted of 21 females and 16 males. There were 7 subjects born at 24 – 28 weeks, 6 at 29 – 31 weeks, and 24 at 32 – 36 weeks. Pulmonary Testing Results: Variable Z Score V1 V2 V2-V1 Male Female GA DLCO -0.17 (-0.59, 0.26) *-0.75 (-1.18, -0.31) *-0.58 (-1.03, -0.12) *-0.86 (-1.42, -0.30) -0.05 (-0.53, 0.43) *0.13 (0.001,0.28) VA 0.06 (-0.24, 0.45) -0.24 (-0.70, 0.23) -0.30 (-0.72 ,0.14) -0.14 (-0.71, 0.43) -0.04 (-0.53, 0.45) 0.09 (-0.05, 0.23) FVC *-0.38 (-0.60, -0.17) **-1.05 (-1.36, -0.74) **-0.67 (-0.98, -0.36) **-0.71 (-1.04, -0.38) **-0.72 (-1.01, -0.44) 0.07 (-0.01, 0.15) FEF50 **-0.88 (-1.15, -0.62) **-1.36 (-1.63, -1.08) *-0.47 (-0.80, -0.14) **-1.12 (-1.44, -0.79) **-1.12 (-1.40, -0.84) **0.15 (0.07,0.23) FEF75 **-0.57 (-0.88, -0.26) **-1.16 (-1.48, -0.83) *-0.59 (-0.93, -0.24) **-0.76 (-1.16, -0.35) **-0.97 (-1.32, -0.62) **0.21 (0.11,0.31) * = p < 0.05 ** = p < 0.001 DLCO was decreased in male subjects compared to female subjects and male full-term infants. VA was not significantly different between subjects and full-term infants. Compared to full-term infants, subjects had decreased forced vital capacity (FVC) and forced expiratory flow at 50% and 75% vital capacity (FEF50 and FEF75). DLCO, FVC, FEF50, and FEF75 exhibited a significant decrease in pulmonary function from V1 to V2 among subjects. Gestational age showed a positive relationship for DLCO, FEF50, and FEF75. Conclusion and Potential Impact: The subjects did not exhibit catch-up growth, or an increase in z score from V1 to V2, in parenchymal and airway function for DLCO, FVC, FEF50, and FEF75. Gestational age and sex were factors affecting pulmonary function. As premature infants are born with lower pulmonary function than full-term infants, it is important to understand how lungs continue to develop after release from the NICU.

Smoking Status Modifies the Relationship between Th2 Biomarkers and Small Airway Obstruction in Asthma

Background. Cigarette smoking and Th2-inflammation are both crucial in the pathogenesis of asthma. However, it is unknown whether smoking can affect the association between Th2-inflammation and small airway obstruction in adults with asthma. Methods. Adults diagnosed with asthma by a pulmonologist according to Global Initiative for Asthma guidelines were recruited from September 2016 to April 2018 to participate in this study. Participants were divided into two groups, the small airway obstruction group (those with FEF25–75% predicted value ≤ 65%) and the normal small airway function group (those with FEF25–75% predicted value > 65%). Final data analysis included 385 and 93 people in the Obstructive Group and the Normal Group, respectively. Total serum IgE level and blood eosinophil count were used as biomarkers of the Th2 phenotype. Results. The Obstructive Group had a larger fraction of smokers, higher blood eosinophil count, and lower lung function than the Normal Group. Current-smoking status was associated with an increased risk of small airway obstruction (adjusted odds ratio = 4.677, 95% confidence interval [1.593–13.730]); and log-IgE level was associated with a decreased risk of small airway obstruction (0.403 [0.216–0.754]). Smoking status stratified analysis showed an association between log-IgE level and a decreased risk of small airway obstruction only in never-smoker asthmatics (0.487 [0.249–0.954]). Conclusions. Current-smoking status and total serum IgE are, respectively, associated with small airway obstruction. Smoking status modifies the relationship between Th2 biomarkers and small airway function. These findings contribute to the understanding of risk factors associated with asthma endotyping.

Asthma as a Developmental Disorder

Asthma is the most common disorder in childhood, affecting six million children in the United States. Asthma is a heterogeneous disease, but most cases either start in early life or have their roots in events occurring in utero or during the preschool years. Protective or harmful exposures, including to environmental microbes, occurring during critical developmental windows determine patterns of immune responses that often persist for a lifetime. Air pollution, tobacco smoke, and prematurity can cause congenital airway narrowing, and newborns with decreased airway function are at risk for having asthma symptoms up to adulthood. Effects of environmental exposures are modified by common genetic variations and may also be mediated by prenatal changes in the epigenetic structure of the genome. Based on this evidence, we have postulated that asthma should be considered a developmental disorder, and this concept may be applicable to other chronic medical conditions affecting both children and adults. Expected final online publication date for the Annual Review of Developmental Psychology, Volume 3 is December 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Small airway function in Finnish COVID-19 survivors

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.

Diagnostic Value of Fractional Exhaled Nitric Oxide and Small Airway Function in Differentiating Cough-Variant Asthma from Typical Asthma

Purpose. To explore the diagnostic value of fractional exhaled nitric oxide (FeNO), small airway function, and a combined of both in differentiating cough-variant asthma (CVA) from typical asthma (TA). Methods. A total of 206 asthma subjects, including 104 CVA and 102 TA, were tested for pulmonary function, bronchial provocation test and FeNO. The correlation between FeNO, small airway function and other pulmonary indicators was analyzed by single correlation and multiple regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate the diagnostic efficiency of FeNO, small airway function, and their combination and to predict the optimal cut-off point. Results. All the respiratory function parameters and small airway function indicators in TA group were significantly different from those in CVA group, and FeNO value was significantly higher than that in CVA group. In addition, the area under the ROC curve (AUC) was estimated to be 0.660 for FeNO, 0.895 for MMEF75%/25%, 0.873 for FEF50%, 0.898 for FEF25%, 0.695 for Fres, 0.650 for R5-R20, and 0.645 for X5. The optimal cut-off points of FeNO, MMEF75%/25%, FEF50%, FEF25%, Fres, R5-R20 and X5, were 48.50 ppb, 60.02%, 63.46%, 45.26%, 16.63 Hz, 0.38 kPa·L−1·s−1, and −1.32, respectively. And the AUC of FeNO combined with small airway function indexes FEF25%, Fres, R5-R20, and X5 were prior than single indicators. Conclusion. FeNO and small airway function indexes might have great diagnostic value for differentiating CVA from TA. The combination of FeNO and FEF25%, Fres, R5-R20, and X5 provided a significantly better prediction than either alone.