Meta-analysis of prevalence of wheezing and recurrent wheezing in infants

Background

Wheezing affects children's quality of life, and is related with asthma in childhood. Although prevalence of wheezing has been previously studied in several countries, there is no reference of worldwide prevalence in infants. The aim of this meta-analysis is to estimate the prevalence of wheezing and recurrent wheezing in infants aged up to two years, and compare the prevalence across world regions.

Persistent wheezing and gastroesophageal reflux in infants

We have evaluated the presence of gastroesophageal reflux (GER) and the effect of its treatment in 12 infants (mean age, 7 months; range, 4–11 months) with persistent wheezing not responding to bronchodilators and anti-inflammatory asthma medications. All patients had GER on cineradiography and significant acid reflux on 24 hour pH monitoring (percentage of time pH < 14 ranged from 6.1 to 47%). All infants were initially treated with prokinetic agents and with receptor histamine antagonists in addition to aggressive pulmonary therapy. Six patients treated medically had substantially decreased use of asthma medications, completely discontinuing them within 2–4 months. Two patients, though significantly improved, require intermittent asthma therapy. Four patients responding poorly to GER and asthma treatment for 2 months to 2 years had fundoplications. These had an excellent outcome over 1–4.5 years follow-up; only one patient required further asthma medications. Pulmonary function testing was done in six patients before and after 6–8 weeks of therapy indicating significant improvement in peripheral airflow: terminal flow/peak tidal expiratory flow (TEF₂₅/PTEF), and percentage of total expiratory time to reach peak tidal expiratory flow (T_p/T_e or T_me/T_e). Our experience suggests that evaluation for GER should be considered in infants with persistent wheezing. Aggressive medical and possibly surgical therapy for GER may resolve persistent wheezing. Pediatr Pulmonol. 1994; 18:39–44. © 1994 Wiley-Liss. Inc.     

Gastroesophageal reflux in infants with wheezing.

The relation between silent gastroesophageal reflux (GER) and respiratory problems such as persistent wheezing in infants is not well-established. Between January 1994 and June 1997, we evaluated the incidence of GER in 84 otherwise healthy infants referred to the Pediatric Pulmonary Medicine Division at Kosair Children's Hospital for evaluation of daily wheezing, and we followed their clinical course for 18 months. All underwent 24-hr esophageal pH studies to evaluate GER. The pH probe study was performed at a mean age of 8.74 +/- 4.6 months. Infants with a positive GER study were treated with an H2 receptor antagonist (H2RA) and a prokinetic agent for a mean of 5.6 +/- 2.4 months. At first follow-up visit 3 weeks after esophageal pH studies infants treated with an H2RA and those who did not have GER but continued with daily wheezing were started on flunisolide nasal solution (0.025%) delivered by nebulizer (125 mcg t.i.d.). Infants in both groups were followed every 1-2 months for a mean of 18 months and if clinically improved, attempts to decrease their daily asthma medications were made. Fifty-four of 84 (64%) had positive esophageal pH studies (GER-positive group), and 24 of them (44%) had no gastrointestinal symptoms suggestive of GER. Thirty patients had normal esophageal pH studies (GER-negative group). Twenty-two of these 30 (73%) infants without GER required nebulized flunisolide, compared to 13 of 54 (24%) infants with GER (P < 0.0005). Thirty-five of 54 (64.8%) infants with GER were able to discontinue all daily asthma medications within 3 months of starting antireflux therapy, while none of the infants without GER were able to discontinue daily asthma medications during the follow-up period (P < 0.0005). We conclude that silent GER is common in infants with daily wheezing, and controlling GER improves morbidity and decreases the need for daily asthma medications.     

A new index to identify risk of multi-trigger wheezing in infants with first episode of wheezing

Objective: Identification of young children who are likely to have multi-trigger wheezing is very important for early diagnosis and treatment of asthma. We investigate an index for predicting multi-trigger wheezing in infants with first episode of wheezing. Methods: One-hundred twenty-eight infants (2–20 months) with first episode of wheezing were followed for two years. Personal and family history of atopic diseases was recorded. Wheezing severity was evaluated using the Preschool Respiratory Assessment Measure. Sputum samples were collected from patients, stained with hematoxylin and eosin and studied by optical microscopy. The largest Creola body in sputum was located and the number of shed exfoliated airway epithelial cells (EAECs) counted. Recurrent wheezing was observed and classified as multi-trigger wheezing or non-multi-trigger wheezing. The predictive value of EAECs, family or personal history of atopic disease and the severity of wheezing for subsequent development of multi-trigger wheezing was analyzed. Results: Better predictive performance was achieved by considering the three measures together than by considering each separately. Receiver operator characteristic analysis showed that an index combining wheezing severity score of 9495 sputum EAECs and a family or personal history of atopic disease had a sensitivity of 95.1%, specificity of 74.2%, a positive predictive value of 58.6% and a negative predictive value of 93.6% for prediction of multi-trigger wheezing. Conclusion: For infants with first episode of wheezing, wheezing severity score, family or personal history of atopic disease and number of EAECs in sputum can predict future multi-trigger wheezing.     

Atopy in wheezing infants always starts with monosensitization.

Previously, evidence has been provided that sensitization is frequent in asthmatic children and polysensitization represents the natural history of allergy. The aim of this study was to investigate whether polysensitization may occur primarily in infants with wheezing. Thus, 98 infants (<1 year of age) were studied at the onset of wheezing symptoms. All children underwent three visits (each including skin-prick test): at baseline and after 2 and 5 years. At onset of wheezing, approximately 20% of infants were sensitized, whereas at 6 years the percentage was >60%. The most important finding was that there was no polysensitized infant at baseline, whereas most of the sensitized children were polysensitized at 6 years. Moreover, the number of sensitizations increased with age. House-dust mites were the most important cause of allergic symptoms. Wheezing may disappear mainly in nonallergic children. In conclusion, this study provided the first evidence that respiratory allergy always starts with monosensitization and confirms previous studies concerning the natural history of allergy characterized by the progression toward polysensitization.     

Lung function in infants with wheezing and gastroesophageal reflux

Eighty-four otherwise healthy infants with daily wheezing underwent infant pulmonary function tests (IPFTs) and 24-h esophageal pH probe studies. Fifty-four (64%) infants had positive pH probe studies, and 30 infants had negative pH probe studies. Many infants in both groups had evidence of peripheral airflow obstruction at tidal breathing and on forced expiration as measured by thoracoabdominal compression. In infants with gastroesophageal reflux (GER), only 9 of 54 (16.6%) responded to bronchodilator therapy compared to 20 of 30 (66.6%) in the group with negative pH probe studies (P < 0.0005). In infants with positive pH studies, family history of asthma (n = 16) correlated well with positive response to bronchodilators (P < 0.0005), and all infants exposed to maternal smoking (n = 11) had no response to bronchodilators. Forty-four percent of infants with a positive pH probe had no gastrointestinal symptoms suggestive of GER. In infants with a negative pH probe, family history of asthma (n = 24) correlated well with positive response to bronchodilators (P < 0.0005), and exposure to maternal smoking (n = 8) correlated well with no response to bronchodilator therapy (P < 0.0005). We conclude that silent GER is common in infants with persistent wheezing. Furthermore, infants with GER are less likely to respond to bronchodilator therapy, and exposure to maternal smoking and family history of asthma may be significant independent factors.     

Impact of the prolonged slow expiratory maneuver on respiratory mechanics in wheezing infants

OBJECTIVE:

To evaluate changes in respiratory mechanics and tidal volume (V_T) in wheezing infants in spontaneous ventilation after performing the technique known as the prolonged, slow expiratory (PSE) maneuver.

METHODS:

We included infants with a history of recurrent wheezing and who had had no exacerbations in the previous 15 days. For the assessment of the pulmonary function, the infants were sedated and placed in the supine position, and a face mask was used and connected to a pneumotachograph. The variables of tidal breathing (V_T and RR) as well as those of respiratory mechanics-respiratory system compliance (Crs), respiratory system resistance (Rrs), and the respiratory system time constant (prs)-were measured before and after three consecutive PSE maneuvers.

RESULTS:

We evaluated 18 infants. The mean age was 32 ± 11 weeks. After PSE, there was a significant increase in V_T (79.3 ± 15.6 mL vs. 85.7 ± 17.2 mL; p = 0.009) and a significant decrease in RR (40.6 ± 6.9 breaths/min vs. 38.8 ± 0,9 breaths/min; p = 0.042). However, no significant differences were found in the variables of respiratory mechanics (Crs: 11.0 ± 3.1 mL/cmH₂O vs. 11.3 ± 2.7 mL/cmH₂O; Rrs: 29.9 ± 6.2 cmH₂O • mL⁻¹ • s⁻¹ vs. 30.8 ± 7.1 cmH₂O • mL⁻¹ • s⁻¹; and prs: 0.32 ± 0.11 s vs. 0.34 ±0.12 s; p > 0.05 for all).

CONCLUSIONS:

This respiratory therapy technique is able to induce significant changes in V_T and RR in infants with recurrent wheezing, even in the absence of exacerbations. The fact that the variables related to respiratory mechanics remained unchanged indicates that the technique is safe to apply in this group of patients. Studies involving symptomatic infants are needed in order to quantify the functional effects of the technique.     

Functional residual capacity and total respiratory system impedance in wheezing infants

Airways obstruction has been demonstrated in acutely wheezing infants. The aim of the present study was to assess functional abnormalities as detected by measurement of total respiratory system resistance (R_rs) and functional residual capacity (FRC) in infants with a history of recurrent episodes of wheezing, while not acutely ill. In 30 such infants (mean age, 10 months; range, 4–17) and in 10 healthy infants (mean age, 6 months; range, 0–14) four R_rs measurements, performed with the forced pseudo-random noise (PRN) oscillation technique, and three FRC determinations, using the closed-circuit helium dilution technique, were averaged. A lower than predicted FRC was demonstrated in 20/30 (66%) patients. At 16 Hz, R_rs was significantly above predicted in 3/30 (10%) patients. Specific R_rs (R_rs × FRC) at 16 Hz was increased in 5/30 (17%) patients. In conclusion, the PRN oscillation technique combined with FRC measurement by helium dilution detects lung function abnormalities in a minority of wheezing infants during symptom-free intervals. Pediatr Pulmonol. 1994; 17:354–358. © 1994 Wiley-Liss, Inc.     

Mannose-binding lectin gene polymorphisms in infants with bronchiolitis and post-bronchiolitis wheezing

BackgroundMannose-binding lectin (MBL) encoded by the MBL2 gene, is an important component of the innate immunity. Low levels have been linked with respiratory infections and both high and low levels with allergy and asthma. The aims of the study were to evaluate the connection between polymorphisms of the MBL2 gene and viral findings, clinical characteristics and subsequent wheezing in young infants with bronchiolitis.MethodsIn all, 129 full-term infants hospitalized for bronchiolitis at age less than 6 months have been followed-up until the mean age of 1.5 years. The genotyping of the MBL2 gene mutations was made by pyrosequencing for a simultaneous detection of three single nucleotide polymorphisms (SNP).ResultsThe MBL genotypes or allele frequencies had no significant associations with clinical characteristics of bronchiolitis. The 41 children with variant genotypes were more often infected by multiple viruses (21.9%, p = 0.047) than children with wild-type A/A genotypes (9.1%). In addition, more children with variant genotypes (31.7%, p = 0.016) had used corticosteroids because of post-bronchiolitis wheezing, compared to those with wild-type A/A genotypes (13.6%). No other significant associations with viral findings or post-bronchiolitis outcomes were found.ConclusionsPreliminary evidence was found that the variant non-A/A genotypes may be associated with susceptibility to multiple viral infections and more severe post-bronchiolitis wheezing requiring treatment with corticosteroids.     

体位改变对喘息婴幼儿潮气呼吸肺功能的影响

目的比较仰卧位和侧卧位两种体位下潮气呼吸肺功能测定结果。方法同时测定在仰卧位和侧卧位下32例喘息患儿的潮气呼吸肺功能,观察肺功能参数变化。结果侧卧位与仰卧位相比潮气呼吸肺功能参数均有改变,差异具有显著性。侧卧位达峰时间比、达峰容积比升高,每千克体重潮气量减少,呼吸频率减慢,吸气时间延长,潮气呼吸峰流速下降。结论体位改变能影响潮气呼吸肺功能检测结果;检测时应统一体位。     

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants

We hypothesized that a new test of infant lung function, less affected by shifts in lung volume, might better detect bronchodilator effects. Using the raised volume forced expiration technique (RVFET), the effect of a bronchodilator on lung function was studied in 22 infants with a history of recurrent wheeze and five healthy infants. Forced expiratory volume in 0.75 s (FEV_0.75), forced expiratory vital capacity (FVC), and forced expiratory flow at 75% of FVC (FEF_75%) were measured by forcing expiration, using an inflatable jacket from a lung volume set by an inspiratory pressure of 20 cm H₂O. A minimum of five measurements were made at baseline and following the administration of 500 μg of salbutamol from a metered dose inhaler via a small volume metal spacer. Changes in lung function in the group of 25 infants who received salbutamol were compared to seven infants who received placebo aerosol. No significant changes occurred in measures of lung function following salbutamol administration when compared to baseline or placebo despite a significant increase in heart rate. A shift in lung volume is unlikely the reason why infants do not demonstrate a change in forced expiration following bronchodilator administration. Pediatr Pulmonol. 1998; 26:35–41. © 1998 Wiley-Liss, Inc.     

Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing

STUDY OBJECTIVE: To determine the cell profile of BAL from infants with severe recurrent wheezing who were not acutely ill at the time of investigation, suggesting an ongoing inflammation. Design and patients: In a retrospective study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32 months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed in children with severe recurrent wheezy bronchitis unresponsive to inhaled steroids. These children were compared with 17 children aged 6 to 36 months (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children were included as control subjects if they had no endobronchial inflammation and no atopy. RESULTS: The BAL cell profile of young children with wheezing typically includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs 313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p = 0.003), as compared with control subjects. The larger number of neutrophils in children with wheezing was not correlated with bacterial or viral infection, or with age, sex, or atopic status. In contrast to the situation in asthmatic adults, eosinophil levels were not higher in children with wheezing than in control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). CONCLUSION: Neutrophil-mediated inflammation in the airways appears to better characterize severe recurrent wheezing in children < 3 years old.