Reduced Lung Function at Birth and the Risk of Asthma at 10 Years of Age

Geir Håland, M.D., Karin C. Lødrup Carlsen, M.D., Ph.D., Leiv Sandvik, Ph.D., Chandra Sekhar Devulapalli, M.D., Monica Cheng Munthe-Kaas, M.D., Morten Pettersen, M.D., Kai-Håkon Carlsen, M.D., Ph.D., for ORAACLE

ABSTRACT

Background Reduced lung function in early infancy has been associated with later obstructive airway diseases. We assessed whether reduced lung function shortly after birth predicts asthma 10 years later.

Methods We conducted a prospective birth cohort study of healthy infants in which we measured lung function shortly after birth with the use of tidal breathing flow-volume loops (the fraction of expiratory time to peak tidal expiratory flow to total expiratory time [t_PTEF/t_E]) in 802 infants and passive respiratory mechanics, including respiratory-system compliance, in 664 infants. At 10 years of age, 616 children (77%) were reassessed by measuring lung function, exercise-induced bronchoconstriction, and bronchial hyperresponsiveness (by means of a methacholine challenge) and by conducting a structured interview to determine whether there was a history of asthma or current asthma.

Results As compared with children whose t_PTEF/t_E shortly after birth was above the median, children whose t_PTEF/t_E was at or below the median were more likely at 10 years of age to have a history of asthma (24.3% vs. 16.2%, P=0.01), to have current asthma (14.6% vs. 7.5%, P=0.005), and to have severe bronchial hyperresponsiveness, defined as a methacholine dose of less than 1.0 µmol causing a 20% fall in the forced expiratory volume in 1 second (FEV₁) (9.1% vs. 4.9%, P=0.05). As compared with children whose respiratory-system compliance was above the median, children with respiratory compliance at or below the median more often had a history of asthma (27.4% vs. 14.8%; P=0.001) and current asthma (15.0% vs. 7.7%, P=0.009), although this measure was not associated with later measurements of lung function. At 10 years of age, t_PTEF/t_E at birth correlated weakly with the maximal midexpiratory flow rate (r=0.10, P=0.01) but not with FEV₁ or forced vital capacity.

Conclusions Reduced lung function at birth is associated with an increased risk of asthma by 10 years of age.

Improving the Management of Chronic Disease at Community Health Centers

Bruce E. Landon, M.D., M.B.A., LeRoi S. Hicks, M.D., M.P.H., A. James O'Malley, Ph.D., Tracy A. Lieu, M.D., M.P.H., Thomas Keegan, Ph.D., Barbara J. McNeil, M.D., Ph.D., and Edward Guadagnoli, Ph.D.

ABSTRACT

Background The Health Disparities Collaboratives of the Health Resources and Services Administration (HRSA) were designed to improve care in community health centers, where many patients from ethnic and racial minority groups and uninsured patients receive treatment.

Methods We performed a controlled preintervention and postintervention study of community health centers participating in quality-improvement collaboratives (the Health Disparities Collaboratives sponsored by the HRSA) for the care of patients with diabetes, asthma, or hypertension. We enrolled 9658 patients at 44 intervention centers that had participated in the collaboratives and 20 centers that had not participated (external control centers). Each intervention center also served as an internal control for another condition. Quality measures were abstracted from medical records at each health center. We created overall quality scores by standardizing and averaging the scores from all of the applicable measures. Changes in quality were evaluated with the use of hierarchical regression models that controlled for patient characteristics.

Results Overall, the intervention centers had considerably greater improvement than the external and internal control centers in the composite measures of quality for the care of patients with asthma and diabetes, but not for those with hypertension. As compared with the external control centers, the intervention centers had significant improvements in the measures of prevention and screening, including a 21% increase in foot examinations for patients with diabetes, and in disease treatment and monitoring, including a 14% increase in the use of antiinflammatory medication for asthma and a 16% increase in the assessment of glycated hemoglobin. There was no improvement, however, in any of the intermediate outcomes assessed (urgent care or hospitalization for asthma, control of glycated hemoglobin levels for diabetes, and control of blood pressure for hypertension).

Conclusions The Health Disparities Collaboratives significantly improved the processes of care for two of the three conditions studied. There was no improvement in the clinical outcomes studied.

Asthma Control during the Year after Bronchial Thermoplasty

Gerard Cox, M.B., Neil C. Thomson, M.D., Adalberto S. Rubin, M.D., Robert M. Niven, M.D., Paul A. Corris, M.D., Hans Christian Siersted, M.D., Ronald Olivenstein, M.D., Ian D. Pavord, M.D., David McCormack, M.D., Rekha Chaudhuri, M.D., John D. Miller, M.D., Michel Laviolette, M.D., for the AIR Trial Study Group

ABSTRACT

Background Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma.

Methods We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting ₂-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed.

Results The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, –0.16±0.37 vs. 0.04±0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3±48.7 vs. 8.5±44.2 liters per minute), scores on the AQLQ (1.3±1.0 vs. 0.6±1.1) and ACQ (reduction, 1.2±1.0 vs. 0.5±1.0), the percentage of symptom-free days (40.6±39.7 vs. 17.0±37.9), and symptom scores (reduction, 1.9±2.1 vs. 0.7±2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment.

Conclusions Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov] .)

Childhood Asthma after Bacterial Colonization of the Airway in Neonates

Hans Bisgaard, M.D., D.M.Sc., Mette Northman Hermansen, M.D., Frederik Buchvald, M.D., Ph.D., Lotte Loland, M.D., Ph.D., Liselotte Brydensholt Halkjaer, M.D., Ph.D., Klaus Bønnelykke, M.D., Martin Brasholt, M.D., Andreas Heltberg, M.D., Nadja Hawwa Vissing, M.D., Sannie Vester Thorsen, M.Sc., Malene Stage, M.Sc., and Christian Bressen Pipper, M.Sc., Ph.D.

ABSTRACT

Background Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.

Methods The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.

Results Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after ₂-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).

Conclusions Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.

A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma

Geoffrey L. Chupp, M.D., Chun Geun Lee, M.D., Ph.D., Nizar Jarjour, M.D., Yun Michael Shim, M.D., Carole T. Holm, R.N., Susan He, M.D., James D. Dziura, Ph.D., M.P.H., Jennifer Reed, Ph.D., Anthony J. Coyle, Ph.D., Peter Kiener, Ph.D., Mark Cullen, M.D., Martine Grandsaigne, Marie-Christine Dombret, M.D., Michel Aubier, M.D., Marina Pretolani, Ph.D., and Jack A. Elias, M.D.

ABSTRACT

Background The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3–like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.

Methods We quantified serum YKL-40 levels in three cohorts of patients with asthma — one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin — as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.

Results Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001)> (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.

Conclusions YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.

Respiratory Effects of Exposure to Diesel Traffic in Persons with Asthma

James McCreanor, M.R.C.P., Paul Cullinan, M.D., Mark J. Nieuwenhuijsen, Ph.D., James Stewart-Evans, M.Sc., Eleni Malliarou, M.Sc., Lars Jarup, Ph.D., Robert Harrington, M.S., Magnus Svartengren, M.D., In-Kyu Han, M.P.H., Pamela Ohman-Strickland, Ph.D., Kian Fan Chung, M.D., and Junfeng Zhang, Ph.D.

ABSTRACT

Background Air pollution from road traffic is a serious health hazard, and people with preexisting respiratory disease may be at increased risk. We investigated the effects of short-term exposure to diesel traffic in people with asthma in an urban, roadside environment.

Methods We recruited 60 adults with either mild or moderate asthma to participate in a randomized, crossover study. Each participant walked for 2 hours along a London street (Oxford Street) and, on a separate occasion, through a nearby park (Hyde Park). We performed detailed real-time exposure, physiological, and immunologic measurements.

Results Participants had significantly higher exposures to fine particles (<2.5> particles, elemental carbon, and nitrogen dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in the forced expiratory volume in 1 second (FEV₁) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that were significantly larger than the reductions in FEV₁ and FVC after exposure in Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure, and P<0.005> greater in subjects with moderate asthma than in those with mild asthma. These changes were accompanied by increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase, 4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter after exposure on Oxford Street; P=0.05) and airway acidification (maximum decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on Oxford Street; P=0.003). The changes were associated most consistently with exposures to ultrafine particles and elemental carbon.

Conclusions Our observations serve as a demonstration and explanation of the epidemiologic evidence that associates the degree of traffic exposure with lung function in asthma

Asthma in Children - Overview

Is this topic for you?

This topic provides information about asthma in children. If you are looking for information about asthma in teens and adults, see the topic Asthma in Teens and Adults.
What is asthma?

Asthma makes it hard for your child to breathe. It causes swelling and inflammation in the airways that lead to the lungs. When asthma flares up, the airways tighten and become narrower. This keeps the air from passing through easily and makes it hard for your child to breathe. These flare ups are also called asthma attacks or exacerbations.

Asthma affects children in different ways. Some children only have asthma attacks during allergy season, when they breathe in cold air, or when they exercise. Others have many bad attacks that send them to the doctor often.

Even if your child has few asthma attacks, you still need to treat the asthma. If the swelling and irritation in your child’s airways isn't controlled, asthma could lower your child's quality of life, prevent your child from exercising, and increase your child's risk of going to the hospital.

Even though asthma is a lifelong disease, treatment can control it and keep your child healthy. Many children with asthma play sports and live healthy, active lives.
What causes asthma?

Experts do not know exactly what causes asthma. But there are some things we do know:
Asthma runs in families. 
Asthma is much more common in people with allergies, though not everyone with allergies gets asthma. And not everyone with asthma has allergies.
Pollution may cause asthma or make it worse.
What are the symptoms?

Symptoms of asthma can be mild or severe. When your child has asthma, he or she may:
Wheeze, making a loud or soft whistling noise that occurs when the airways narrow.
Cough a lot.
Feel tightness in the chest.
Feel short of breath.
Have trouble sleeping because of coughing and wheezing.
Quickly get tired during exercise.

Many children with asthma have symptoms that are worse at night.
How is asthma diagnosed?

Along with doing a physical exam and asking about your child’s symptoms, your doctor may order tests such as:
Spirometry. Doctors use this test to diagnose and keep track of asthma in children age 5 and older. It measures how quickly your child can move air in and out of the lungs and how much air is moved. Spirometry is not used with babies and small children. In those cases, the doctor usually will listen for wheezing and will ask how often the child wheezes or coughs.
Peak expiratory flow (PEF). This shows how fast your child can breathe out when trying his or her hardest.
A chest X-ray to see if another disease is causing your child’s symptoms.
Allergy tests, if your doctor thinks your child’s symptoms may be caused by allergies.