Asthma Journal Scan, 2005 Year in Review
Asthma Journal Scan, 2005 Year in Review
Author's Note:
It is a daunting task to pick 10 articles, published over the last year, that had an important impact on those caring for patients with asthma and related diseases. It would be much easier to pick the 50 or 100 most important articles, rather than 10. I could also easily argue for a different list of articles, as the medical literature is rich with significant research contributions, many of which have added important observations to this area of medicine. An entirely different list could also be made for important basic science contributions; however, this summary focuses on those publications that emphasize patient care in the context of clinical medicine. So it is with significant humility that I list 10 such articles, chosen for their contribution to patient care, or their unique observations; some of which open up new discussions and debates regarding previously held assumptions.
Journal of Allergy and Clinical Immunology
December 2005 (Volume 116, Number 6)
Irreversible Lung Function Deficits in Young Adults With a History of Childhood Asthma
Limb SL, Brown KC, Wood RA, et al
J Allergy Clin Immunol. 2005;116:1213-1219
Although asthma has historically been considered "reversible airway obstruction," we now know that there is a subset of patients with asthma who develop irreversible airway obstruction. The current catch phrase for this phenomenon is "airway remodeling." It amounts to "airway scarring," and is not reversible with asthma pharmacotherapy, including inhaled and oral corticosteroids. This irreversible airway obstruction is now known to occur in some patients with asthma, regardless of their past smoking status.
These authors conducted this follow-up study in patients from the Childhood Asthma Study (CAS), a group of young asthmatics previously enrolled in a randomized trial of immunotherapy for childhood asthma. They went back and tried to recruit the 121 patients originally enrolled in the CAS trial and were able to get 84 patients back to be re-evaluated. Their goal was to assess the frequency, severity, and reversibility of pulmonary function deficits in adults who have a known history of moderate-to-severe childhood allergic asthma. These patients were now aged 17-30 years, and those who had a postbronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), or FEV1/FVC ratio less than or equal to the fifth percentile or who had 2 or more indices less than the 10th percentile (using National Health and Nutrition Examination Survey III normative data) were invited for further evaluation. This subsequent assessment included complete pulmonary function testing, physical examination, and a chest radiograph after they had received 1 week of oral prednisone dosed daily at 1 mg/kg.
The researchers found that nearly half (48%) of these patients had 1 or more spirometric indices that were less than or equal to the fifth and 10th percentiles, respectively (P < .0001). Of those 28 patients reassessed after they had received the prednisone treatment, 75% had not improved. There was a significant relationship between spirometry results in childhood and those subsequently found in adulthood (P < .001). There were several factors that correlated with the finding of adults with persistently abnormal spirometry. These risk factors included a longer duration of asthma at enrollment in the original (childhood) asthma study, increased childhood sensitivity to inhaled methacholine (indicating heightened bronchial hyperresponsiveness), as well as premature birth. Those who were born prematurely were over 10 times more likely to have irreversible airway obstruction as an adult, compared with those who were not born prematurely.
The authors concluded that many adults with a history of moderate to severe allergic asthma as a child have irreversible airway obstruction once they reach adulthood. They also recommend that such individuals to be identified at higher risk of irreversible airway obstruction once they reach adulthood (ie, with more severe childhood airway obstruction, a longer duration of asthma, increased methacholine sensitivity, and premature birth) could perhaps be identified sooner as children, when perhaps closer attention and further research might allow us to halt this process before it becomes irreversible.
Abstract
January 2005 (Volume 115, Number 1)
NAEPP Expert Panel Report. Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment -- 2004 Update
J Allergy Clin Immunol. 2005;115:34-46
Managing asthma during pregnancy always makes a physician pause for a moment, pondering the risk/benefit ratio of treatment decisions for both the mother and baby. Specific prevalence data have now suggested that asthma during pregnancy is increasing, affecting between 3.8% and 8.4% of this population. Some researchers have suggested that asthma is often undertreated by both physicians and patients for fear of adverse fetal effects of maternal medication.
Appropriate management of asthma during pregnancy is very important, since a recent study suggested that those pregnant patients experiencing daily asthma symptoms have an elevated risk of pre-eclampsia, and, in addition, those expectant mothers with increased asthma symptoms or lower pulmonary function may have reduced fetal growth. There have been several studies suggesting the safety of inhaled short-acting beta agonists such as albuterol as well as inhaled corticosteroids (ICS), especially budesonide, during pregnancy. Appropriate use of ICS helps prevent acute asthma exacerbations during pregnancy; however, some newer data are not as reassuring about the use of oral corticosteroids (OCS), with those using OCS possibly showing a slight increase in the risk of pre-eclampsia, prematurity, and oral clefts. Nonetheless, if patients with asthma require oral corticosteroids as per national treatment guidelines, they should be treated as such, since the risk of untreated asthma is significantly greater than the risk of side effects from asthma medications.
All physicians who care for women of childbearing age should be familiar with the newly released National Asthma Education and Prevention Program (NAEPP) Expert Panel Report entitled: "Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment -- 2004 Update." The report is based on evidence when it is available, and when it is not, then expert consensus opinion is used to establish recommendations. This is the current update of the last set of NAEPP recommendations for asthma management during pregnancy issued in 1993. Since then, there have been some changes based on new data. Asthma management is organized around 4 key components:
This is an excellent review of this important topic, and all are encouraged to read through and incorporate these revised recommendations into practice.
Abstract
March 2005 (Volume 115, Number 3)
Relationship of Validated Psychometric Tools to Subsequent Medical Utilization for Asthma
Schatz M, Mosen D, Apter AJ, et al
J Allergy Clin Immunol. 2005;115:564-570
Both patients and physicians are often surprised by exacerbations of asthma that result in the need for emergent management in the emergency department or hospital. It is well known that several factors may contribute to these exacerbations. First, asthma is a disease whose symptoms often vary in severity over time, and asthma symptom severity may be affected by environmental exposures, medication compliance, and other factors. To complicate matters further, some patients are poor perceivers of their respiratory symptoms. These "poor perceivers" may experience increasing airway obstruction with little or no increase in their perceived dyspnea, and as airway obstruction becomes severe, they may suddenly note severe dyspnea seemingly occurring "out of the blue," and resulting in the need for emergent asthma care.
This group of researchers sought to identify patients who might be at increased risk for emergent asthma care by using 4 validated psychometric tests. These tools measured generic quality of life (both physical and mental components), asthma-specific quality of life, asthma control, and asthma symptom severity. Results of these questionnaires were linked to administrative databases in the Kaiser Permanente Health Care system in northern California and Oregon. In this way, healthcare utilization (including emergency department and hospital use), as well as short-acting beta-agonist use and oral corticosteroid therapy (for that year and the year following the survey), could be followed.
Using univariate analysis, the researchers found that the scores for each psychometric test were significantly related to subsequent healthcare utilization. Patients with higher scale-defined morbidity on these psychometric tests were as much as 4 times more likely to need emergent healthcare in the hospital or emergency department for asthma. The authors concluded that validated psychometric tools appeared to be useful for stratifying risk of healthcare utilization and increased asthma morbidity if other utilization and demographic predictors are not available. Such tools may be helpful to help identify those who may need extra attention with their asthma treatment programs, so that more severe asthma exacerbations might be prevented.
Abstract
July 2005 (Volume 116, Number 1)
The Canadian Childhood Asthma Primary Prevention Study: Outcomes at 7 Years of Age
Chan-Yeung M, Ferguson A, Watson W, et al
J Allergy Clin Immunol. 2005;116:49-55
Since the incidence of asthma has been increasing in many areas of the world over the last several decades, effective strategies for both asthma treatment and prevention have been increasingly sought by researchers. These efforts have been somewhat thwarted by the complexity of this disease, which has both genetic and environmental factors contributing to disease expression. Results achieved by targeting any 1 specific risk factor for intervention have been somewhat disappointing.
These researchers studied a multifaceted intervention program to attempt to prevent the development of asthma in high-risk infants. These children were followed from before birth until age 7 years, and 545 high-risk infants with an immediate family history of asthma and allergies were randomized prospectively into intervention or control groups prenatally. The intervention group had changes instituted before they were even born. Strategies employed included avoidance of house dust, pets, environmental tobacco smoke, and encouragement of breast feeding with delayed introduction of solid foods. At age 7 years, the children were examined by pediatric allergists and had allergy skin tests as well as methacholine challenge tests.
When the 380 children available for follow-up were seen back for assessment at age 7 years, the prevalence of pediatric allergist-diagnosed asthma, defined as wheeze without colds and concomitant increased bronchial hyperresponsiveness, was significantly lower in the intervention group (14.9%) compared with the control group (23.0%) (adjusted risk ratio 0.44; 95% CI 0.25-0.79). There was not a significant difference between the 2 groups in the incidence of allergic rhinitis, atopic dermatitis, atopy (as defined by positive allergy skin tests to any common allergen), or bronchial hyperresponsiveness as measured by methacholine. The authors concluded that the multifaceted intervention approach was effective in reducing the development of asthma in children by the age of 7 years.
This is a very important study because it puts some earlier studies (which have looked at only a single intervention to try to prevent asthma) into perspective. These earlier studies have found that a single intervention may have been ineffective at preventing the development of asthma. These investigators show us that a comprehensive and coordinated program is much more likely to have the greatest success in preventing the development of lower respiratory disease in this population.
Abstract
September 2005 (Volume 116, Number 3)
Nature of Airway Inflammation and Remodeling in Chronic Cough
Niimi A, Torrego A, Nicholson AG, Cosio, Oates TB, Chung KF
J Allergy Clin Immunol. 2005;116:565-570
Physicians often face the frustrating task of trying to unravel the potential causes of a stubborn chronic cough. Chronic cough may have a number of etiologies, including postnasal drip, gastroesophageal reflux disease (GERD), and cough-variant asthma. In some patients, no etiologic factor can be identified. These investigators studied 33 patients suffering from chronic cough, including 6 with postnasal drip/rhinitis, 5 with GERD, 3 with bronchiectasis, 19 with idiopathic cough, and 14 with asthmatic cough. They also studied 15 healthy controls. In these various research subjects, they performed bronchoscopy with biopsy as well as capsaicin cough sensitivity testing on all patients.
They found that patients with cough due to asthma had greater numbers of submucosal eosinophils and neutrophils (P < .005 compared with other groups), and that those with nonasthmatic cough had higher levels of submucosal mast cells compared with the others (P < .01). Of note, thickening in the subbasement membrane area as well as increased goblet cells, vascularity, and blood vessel size were also noted in both those with asthmatic cough and those with nonasthmatic cough. In contrast, smooth muscle area was greater only in those with nonasthmatic cough compared with asthmatic cough and the control group. None of the changes seen on biopsy correlated with the duration of the cough. Also of note, patients with nonasthmatic cough had a heightened cough reflex compared with those with asthmatic cough or the control group. Those in the nonasthmatic group (with greater goblet cell hyperplasia and greater epithelial shedding) had increased cough sensitivity to capsaicin.
The authors concluded that airway remodeling can take place in patients with chronic cough, even in the absence of apparent asthma. The remodeling seems to be more closely related to the chronic cough rather than just the presence of demonstrable asthma. It is also noteworthy that bronchial biopsies from patients with nonasthmatic cough may show mast cell hyperplasia. These findings are important because they highlight the attention that needs to be paid to adequate treatment for patients with chronic cough. It is not yet clear, however, whether appropriate treatment of the cough will have any impact on the trajectory of possible airway remodeling.
Abstract
Airway Immunopathology of Asthma With Exercise-induced Bronchoconstriction
Hallstrand TS, Moody MW, Aitken ML, Henderson WR
J Allergy Clin Immunol. 2005;116:586-593
Exercise-induced bronchoconstriction (EIB) is experienced by the majority of patients with asthma, and it has typically been considered something that was treated with pre-exercise (or "as needed") bronchodilators. It is now becoming apparent that EIB is more complex than we originally realized. First, there are clearly some patients who have more significant EIB than one would expect from their baseline pulmonary function or from their bronchial hyperresponsiveness testing (as measured by methacholine responsiveness). These investigators conducted a comparative immunopathology study of 2 groups of asthmatics (1 with and 1 without EIB) and used induced sputum to characterize differences in lower airway inflammation as well as looking at the production of various cytokines and eicosanoids.
The 2 groups had similar lung function at baseline and had not had an exacerbation of asthma in the prior year. Several differences emerged when those with and without significant EIB had their sputum analyzed. When analyzing expectorated sputum, those with EIB had more desquamated columnar epithelial cells, more eosinophils, more cysteinyl leukotrienes, and the ratio of cysteinyl leukotrienes to prostaglandin E2 was greater in those with EIB.
The researchers concluded that there was significant evidence to show airway inflammation and injury in patients with EIB. Further research demonstrating the varying effectiveness of different treatment programs (geared toward minimizing this airway injury) would be helpful in clarifying the appropriate management of these patients.
These finding may help explain why some patients with EIB tend to do better once they are treated with ICS. Perhaps there is more of an inflammatory component to EIB than we originally appreciated.
Abstract
Annals of Allergy, Asthma, & Immunology
July 2005 (Volume 95, Number 1)
Asthma Morbidity and Treatment in the Chicago Metropolitan Area: One Decade After National Guidelines
Grant EN, Malone A, Lyttle CS, Weiss KB
Ann Allergy Asthma Immunol. 2005;95:19-25
Although there have been numerous studies investigating the overall asthma morbidity and mortality data for countries as a whole, it is uncommon to see population-based asthma hospitalization and emergency department data for a specific urban area, especially one recognized as having significant morbidity from asthma. These investigators examined the burden of asthma care using a population-based study in the greater Chicago, Illinois, metropolitan area and also attempted to identify demographic and social influences on asthma morbidity and treatment practices.
They conducted a telephone survey of adults in the greater Chicago area between 1999 and 2000 and ended up with 152 adults and children with active asthma. Twenty-five percent of these respondents reported emergency department use and 6.6% required hospitalization in the previous year. Despite these significant healthcare utilization numbers, less than one third reported regular use of asthma controller medications. After the investigators adjusted for age, sex, income, education, and reported current pharmacotherapy, there was a significant race difference in healthcare utilization. Compared with white individuals, African American individuals were 6.3 times more likely to have been treated in the emergency department and over 12 times more likely to have required hospitalization for asthma treatment.
The authors conclude that despite very clear instructions in clinically effective national asthma treatment guidelines such as the National Asthma Education and Prevention Program, poorly controlled asthma remains a significant problem in this metropolitan area (and most likely many others as well). The racial discrepancies in healthcare utilization warrant further study so that factors contributing to this finding can also be further elucidated and addressed.
Abstract
Thorax
June 2005 (Volume 60, Number 6)
Patients With Gastro-oesophageal Reflux Disease and Cough Have Impaired Laryngopharyngeal Mechanosensitivity
Phua SY, McGarvey LP, Ngu MC, Ing AJ
Thorax. 2005;60:488-491
The act of swallowing is a highly sophisticated, complex series of coordinated muscular contractions that move food and secretions from the mouth into the esophagus. If there is a problem somewhere in this orchestrated series of events, then aspiration into the airway may occur. One of the common complications of GERD is chronic cough -- cough that may potentially be caused by several possible mechanisms, including neurologic (ie, vagal) reflexes, laryngeal irritation, or possibly aspiration. Appropriate sensitivity of the laryngopharyngeal structures helps prevent aspiration. If this sensitivity is impaired, then the sensory feedback given by these laryngeal structures used in the act of swallowing could be abnormal.
These authors measured laryngopharyngeal sensitivity (LPS) in 15 patients by using fiber optic endoscopic evaluation of swallowing with sensory testing. This LPS testing is a technique that utilizes the delivery of air pulses to the aryepiglottic folds, eliciting a laryngeal adductor reflex (LAR). LPS is measured by finding the lowest air pressure to elicit the LAR. The study subjects then had either normal saline or 0.1 N hydrochloric acid infused into the laryngopharyngeal area.
They found that the mean LAR threshold was elevated in those with GERD and chronic cough; an elevated threshold indicates decreased sensitivity of the laryngeal structures. Of note, the infusion of hydrochloric acid also elevated the LAR threshold, whereas infusion of saline failed to cause any change in the sensitivity of the laryngopharyngeal area. The authors concluded that chronic exposure of these laryngeal structures to gastric acid may decrease the sensitivity of this anatomic area, with an accompanying increased risk of aspiration.
Abstract
The New England Journal of Medicine
May 19, 2005 (Volume 352, Number 20)
Asthma as a Risk Factor for Invasive Pneumococcal Disease
Talbot TR, Hartert TV, Mitchel E, et al
N Engl J Med. 2005;352:2082-2090
Invasive infection with Streptococcus pneumoniae is more common among people known to be at high risk for severe infection. These patients may include those with a number of medical conditions, including those infected with HIV, as well as those with diabetes mellitus, sickle cell disease, renal disease, hepatic disease (including cirrhosis), chronic obstructive pulmonary disease (COPD), cancer, and immunosuppression due to illness or medications such as chronic corticosteroids, tobacco use, and alcohol abuse. In contrast to the known increase in the risk of invasive pneumococcal disease in patients with COPD, the risk among patients with asthma is not known. Current asthma treatment guidelines do not recommend pneumococcal vaccination as an infection prevention strategy, and current guidelines for pneumococcal vaccination specifically exclude people with asthma. Since approximately 7% to 10% of the US population has asthma, and this percentage appears to be increasing, these authors set out to determine if the incidence of invasive pneumococcal disease was higher in patients with asthma. They conducted a nested, case-control study using data from 2 large, population-based databases. After they analyzed the association, they conducted a cohort analysis to determine the incidence of invasive pneumococcal disease in people with and without asthma who were enrolled in Tennessee's Medicaid program (TennCare).
They matched 10 control patients without invasive pneumococcal disease for every patient with invasive pneumococcal disease, and studied 635 patients and 6350 controls. A total of 114 patients (18%) had asthma. Patients with asthma were nearly 2.5 times more likely to have invasive pneumococcal disease than those without asthma (adjusted odds ratio 2.4; 95% CI 1.9-3.1). The authors concluded that asthma is an independent risk factor for invasive pneumococcal disease, and that the risk among patients with asthma is at least double that of controls. I would assume that these data will most likely be taken into account in future versions of both pneumococcal vaccination and asthma treatment guidelines, with a possible change in the guidelines to suggest the need for pneumococcal vaccination in patients with asthma.
Abstract
April 14, 2005 (Volume 352, Number 15)
Daily Versus As-Needed Corticosteroids for Mild Persistent Asthma
Boushey HA, Sorkness CA, King TS, et al
N Engl J Med. 2005;352:1519-1528
The National Asthma Education and Prevention Program (NAEPP/NIH) Expert Panel Guidelines for the Diagnosis and Management of Asthma divides asthma severity into 4 categories: mild intermittent; and mild, moderate, and severe persistent asthma. Optimal therapy is determined by matching treatment intensity with a patient's asthma severity classification. At the present time, the NAEPP/NIH guidelines recommend regular treatment with an ICS for those patients who have mild persistent asthma. This trial, called the Improving Asthma Control (IMPACT) trial, compared the level of asthma control achieved using regular vs intermittent "as needed" treatment with a controller medication (either an ICS [budesonide] or a leukotriene-receptor antagonist [LTRA, zafirlukast]). The primary outcome measure was morning peak expiratory flow rate (AM PEFR), and secondary outcomes included the frequency of asthma exacerbations, number of days lost from work or school, number of symptom-free days, asthma-related quality of life, and a panel of physiological and biologic measures of asthma activity.
This was a double-blind trial of 225 adults who received an ICS, an LTRA, or placebo. Although rates of exacerbations and AM PEFR were similar among the 3 groups, those treated with daily budesonide had better scores for asthma control, less bronchial hyperreactivity, less exhaled nitric oxide (suggesting less inflammation), greater improvements in prebronchodilator FEV1, less sputum eosinophilia, and more symptom-free days. Those treated with daily zafirlukast did not differ significantly from those treated intermittently. There was not a significant difference among the groups for postbronchodilator scores or quality of life. Patients in the budesonide group reported 26 more days free from symptoms per year compared with the other groups.
This interesting study looks at an important question. Because studies have shown that patients frequently do not comply with asthma medications as instructed, and often do not get into serious trouble with asthma exacerbations, it asks whether we should be looking at intermittent (vs daily) anti-inflammatory therapy in those with mild asthma. Some of the results of the study were somewhat surprising; namely, that the asthma exacerbation rate among the 3 study groups was similar. The other findings, however, including the significant improvements seen in the daily budesonide group, were consistent with what one would expect. This study, which was well structured and conducted, raises some important questions. In my view, however, as well as those of the authors, this should be considered a study to raise the question regarding the appropriateness of intermittent anti-inflammatory treatment for mild persistent asthma. I believe additional studies addressing this question are needed before the treatment guidelines and clinical practice should be changed from their current recommendation of daily anti-inflammatory therapy for mild persistent asthma.
Abstract
Author's Note:
It is a daunting task to pick 10 articles, published over the last year, that had an important impact on those caring for patients with asthma and related diseases. It would be much easier to pick the 50 or 100 most important articles, rather than 10. I could also easily argue for a different list of articles, as the medical literature is rich with significant research contributions, many of which have added important observations to this area of medicine. An entirely different list could also be made for important basic science contributions; however, this summary focuses on those publications that emphasize patient care in the context of clinical medicine. So it is with significant humility that I list 10 such articles, chosen for their contribution to patient care, or their unique observations; some of which open up new discussions and debates regarding previously held assumptions.
Journal of Allergy and Clinical Immunology
December 2005 (Volume 116, Number 6)
Irreversible Lung Function Deficits in Young Adults With a History of Childhood Asthma
Limb SL, Brown KC, Wood RA, et al
J Allergy Clin Immunol. 2005;116:1213-1219
Although asthma has historically been considered "reversible airway obstruction," we now know that there is a subset of patients with asthma who develop irreversible airway obstruction. The current catch phrase for this phenomenon is "airway remodeling." It amounts to "airway scarring," and is not reversible with asthma pharmacotherapy, including inhaled and oral corticosteroids. This irreversible airway obstruction is now known to occur in some patients with asthma, regardless of their past smoking status.
These authors conducted this follow-up study in patients from the Childhood Asthma Study (CAS), a group of young asthmatics previously enrolled in a randomized trial of immunotherapy for childhood asthma. They went back and tried to recruit the 121 patients originally enrolled in the CAS trial and were able to get 84 patients back to be re-evaluated. Their goal was to assess the frequency, severity, and reversibility of pulmonary function deficits in adults who have a known history of moderate-to-severe childhood allergic asthma. These patients were now aged 17-30 years, and those who had a postbronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), or FEV1/FVC ratio less than or equal to the fifth percentile or who had 2 or more indices less than the 10th percentile (using National Health and Nutrition Examination Survey III normative data) were invited for further evaluation. This subsequent assessment included complete pulmonary function testing, physical examination, and a chest radiograph after they had received 1 week of oral prednisone dosed daily at 1 mg/kg.
The researchers found that nearly half (48%) of these patients had 1 or more spirometric indices that were less than or equal to the fifth and 10th percentiles, respectively (P < .0001). Of those 28 patients reassessed after they had received the prednisone treatment, 75% had not improved. There was a significant relationship between spirometry results in childhood and those subsequently found in adulthood (P < .001). There were several factors that correlated with the finding of adults with persistently abnormal spirometry. These risk factors included a longer duration of asthma at enrollment in the original (childhood) asthma study, increased childhood sensitivity to inhaled methacholine (indicating heightened bronchial hyperresponsiveness), as well as premature birth. Those who were born prematurely were over 10 times more likely to have irreversible airway obstruction as an adult, compared with those who were not born prematurely.
The authors concluded that many adults with a history of moderate to severe allergic asthma as a child have irreversible airway obstruction once they reach adulthood. They also recommend that such individuals to be identified at higher risk of irreversible airway obstruction once they reach adulthood (ie, with more severe childhood airway obstruction, a longer duration of asthma, increased methacholine sensitivity, and premature birth) could perhaps be identified sooner as children, when perhaps closer attention and further research might allow us to halt this process before it becomes irreversible.
Abstract
January 2005 (Volume 115, Number 1)
NAEPP Expert Panel Report. Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment -- 2004 Update
J Allergy Clin Immunol. 2005;115:34-46
Managing asthma during pregnancy always makes a physician pause for a moment, pondering the risk/benefit ratio of treatment decisions for both the mother and baby. Specific prevalence data have now suggested that asthma during pregnancy is increasing, affecting between 3.8% and 8.4% of this population. Some researchers have suggested that asthma is often undertreated by both physicians and patients for fear of adverse fetal effects of maternal medication.
Appropriate management of asthma during pregnancy is very important, since a recent study suggested that those pregnant patients experiencing daily asthma symptoms have an elevated risk of pre-eclampsia, and, in addition, those expectant mothers with increased asthma symptoms or lower pulmonary function may have reduced fetal growth. There have been several studies suggesting the safety of inhaled short-acting beta agonists such as albuterol as well as inhaled corticosteroids (ICS), especially budesonide, during pregnancy. Appropriate use of ICS helps prevent acute asthma exacerbations during pregnancy; however, some newer data are not as reassuring about the use of oral corticosteroids (OCS), with those using OCS possibly showing a slight increase in the risk of pre-eclampsia, prematurity, and oral clefts. Nonetheless, if patients with asthma require oral corticosteroids as per national treatment guidelines, they should be treated as such, since the risk of untreated asthma is significantly greater than the risk of side effects from asthma medications.
All physicians who care for women of childbearing age should be familiar with the newly released National Asthma Education and Prevention Program (NAEPP) Expert Panel Report entitled: "Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment -- 2004 Update." The report is based on evidence when it is available, and when it is not, then expert consensus opinion is used to establish recommendations. This is the current update of the last set of NAEPP recommendations for asthma management during pregnancy issued in 1993. Since then, there have been some changes based on new data. Asthma management is organized around 4 key components:
Assessment and monitoring of asthma, including objective measures of pulmonary function; spirometry is preferred;
Control of factors contributing to asthma severity, such as allergens and irritants, including tobacco smoke;
Patient education, including self-monitoring in some patients, proper use of inhalers, and instructions on how to handle worsening asthma symptoms; and
A stepwise approach to pharmacologic therapy, using the national treatment guidelines.
This is an excellent review of this important topic, and all are encouraged to read through and incorporate these revised recommendations into practice.
Schatz M. Breathing for two: now we can all breathe a little easier. J Allergy Clin Immunol. 2005;115:31-33.
Abstract
March 2005 (Volume 115, Number 3)
Relationship of Validated Psychometric Tools to Subsequent Medical Utilization for Asthma
Schatz M, Mosen D, Apter AJ, et al
J Allergy Clin Immunol. 2005;115:564-570
Both patients and physicians are often surprised by exacerbations of asthma that result in the need for emergent management in the emergency department or hospital. It is well known that several factors may contribute to these exacerbations. First, asthma is a disease whose symptoms often vary in severity over time, and asthma symptom severity may be affected by environmental exposures, medication compliance, and other factors. To complicate matters further, some patients are poor perceivers of their respiratory symptoms. These "poor perceivers" may experience increasing airway obstruction with little or no increase in their perceived dyspnea, and as airway obstruction becomes severe, they may suddenly note severe dyspnea seemingly occurring "out of the blue," and resulting in the need for emergent asthma care.
This group of researchers sought to identify patients who might be at increased risk for emergent asthma care by using 4 validated psychometric tests. These tools measured generic quality of life (both physical and mental components), asthma-specific quality of life, asthma control, and asthma symptom severity. Results of these questionnaires were linked to administrative databases in the Kaiser Permanente Health Care system in northern California and Oregon. In this way, healthcare utilization (including emergency department and hospital use), as well as short-acting beta-agonist use and oral corticosteroid therapy (for that year and the year following the survey), could be followed.
Using univariate analysis, the researchers found that the scores for each psychometric test were significantly related to subsequent healthcare utilization. Patients with higher scale-defined morbidity on these psychometric tests were as much as 4 times more likely to need emergent healthcare in the hospital or emergency department for asthma. The authors concluded that validated psychometric tools appeared to be useful for stratifying risk of healthcare utilization and increased asthma morbidity if other utilization and demographic predictors are not available. Such tools may be helpful to help identify those who may need extra attention with their asthma treatment programs, so that more severe asthma exacerbations might be prevented.
Abstract
July 2005 (Volume 116, Number 1)
The Canadian Childhood Asthma Primary Prevention Study: Outcomes at 7 Years of Age
Chan-Yeung M, Ferguson A, Watson W, et al
J Allergy Clin Immunol. 2005;116:49-55
Since the incidence of asthma has been increasing in many areas of the world over the last several decades, effective strategies for both asthma treatment and prevention have been increasingly sought by researchers. These efforts have been somewhat thwarted by the complexity of this disease, which has both genetic and environmental factors contributing to disease expression. Results achieved by targeting any 1 specific risk factor for intervention have been somewhat disappointing.
These researchers studied a multifaceted intervention program to attempt to prevent the development of asthma in high-risk infants. These children were followed from before birth until age 7 years, and 545 high-risk infants with an immediate family history of asthma and allergies were randomized prospectively into intervention or control groups prenatally. The intervention group had changes instituted before they were even born. Strategies employed included avoidance of house dust, pets, environmental tobacco smoke, and encouragement of breast feeding with delayed introduction of solid foods. At age 7 years, the children were examined by pediatric allergists and had allergy skin tests as well as methacholine challenge tests.
When the 380 children available for follow-up were seen back for assessment at age 7 years, the prevalence of pediatric allergist-diagnosed asthma, defined as wheeze without colds and concomitant increased bronchial hyperresponsiveness, was significantly lower in the intervention group (14.9%) compared with the control group (23.0%) (adjusted risk ratio 0.44; 95% CI 0.25-0.79). There was not a significant difference between the 2 groups in the incidence of allergic rhinitis, atopic dermatitis, atopy (as defined by positive allergy skin tests to any common allergen), or bronchial hyperresponsiveness as measured by methacholine. The authors concluded that the multifaceted intervention approach was effective in reducing the development of asthma in children by the age of 7 years.
This is a very important study because it puts some earlier studies (which have looked at only a single intervention to try to prevent asthma) into perspective. These earlier studies have found that a single intervention may have been ineffective at preventing the development of asthma. These investigators show us that a comprehensive and coordinated program is much more likely to have the greatest success in preventing the development of lower respiratory disease in this population.
Abstract
September 2005 (Volume 116, Number 3)
Nature of Airway Inflammation and Remodeling in Chronic Cough
Niimi A, Torrego A, Nicholson AG, Cosio, Oates TB, Chung KF
J Allergy Clin Immunol. 2005;116:565-570
Physicians often face the frustrating task of trying to unravel the potential causes of a stubborn chronic cough. Chronic cough may have a number of etiologies, including postnasal drip, gastroesophageal reflux disease (GERD), and cough-variant asthma. In some patients, no etiologic factor can be identified. These investigators studied 33 patients suffering from chronic cough, including 6 with postnasal drip/rhinitis, 5 with GERD, 3 with bronchiectasis, 19 with idiopathic cough, and 14 with asthmatic cough. They also studied 15 healthy controls. In these various research subjects, they performed bronchoscopy with biopsy as well as capsaicin cough sensitivity testing on all patients.
They found that patients with cough due to asthma had greater numbers of submucosal eosinophils and neutrophils (P < .005 compared with other groups), and that those with nonasthmatic cough had higher levels of submucosal mast cells compared with the others (P < .01). Of note, thickening in the subbasement membrane area as well as increased goblet cells, vascularity, and blood vessel size were also noted in both those with asthmatic cough and those with nonasthmatic cough. In contrast, smooth muscle area was greater only in those with nonasthmatic cough compared with asthmatic cough and the control group. None of the changes seen on biopsy correlated with the duration of the cough. Also of note, patients with nonasthmatic cough had a heightened cough reflex compared with those with asthmatic cough or the control group. Those in the nonasthmatic group (with greater goblet cell hyperplasia and greater epithelial shedding) had increased cough sensitivity to capsaicin.
The authors concluded that airway remodeling can take place in patients with chronic cough, even in the absence of apparent asthma. The remodeling seems to be more closely related to the chronic cough rather than just the presence of demonstrable asthma. It is also noteworthy that bronchial biopsies from patients with nonasthmatic cough may show mast cell hyperplasia. These findings are important because they highlight the attention that needs to be paid to adequate treatment for patients with chronic cough. It is not yet clear, however, whether appropriate treatment of the cough will have any impact on the trajectory of possible airway remodeling.
Abstract
Airway Immunopathology of Asthma With Exercise-induced Bronchoconstriction
Hallstrand TS, Moody MW, Aitken ML, Henderson WR
J Allergy Clin Immunol. 2005;116:586-593
Exercise-induced bronchoconstriction (EIB) is experienced by the majority of patients with asthma, and it has typically been considered something that was treated with pre-exercise (or "as needed") bronchodilators. It is now becoming apparent that EIB is more complex than we originally realized. First, there are clearly some patients who have more significant EIB than one would expect from their baseline pulmonary function or from their bronchial hyperresponsiveness testing (as measured by methacholine responsiveness). These investigators conducted a comparative immunopathology study of 2 groups of asthmatics (1 with and 1 without EIB) and used induced sputum to characterize differences in lower airway inflammation as well as looking at the production of various cytokines and eicosanoids.
The 2 groups had similar lung function at baseline and had not had an exacerbation of asthma in the prior year. Several differences emerged when those with and without significant EIB had their sputum analyzed. When analyzing expectorated sputum, those with EIB had more desquamated columnar epithelial cells, more eosinophils, more cysteinyl leukotrienes, and the ratio of cysteinyl leukotrienes to prostaglandin E2 was greater in those with EIB.
The researchers concluded that there was significant evidence to show airway inflammation and injury in patients with EIB. Further research demonstrating the varying effectiveness of different treatment programs (geared toward minimizing this airway injury) would be helpful in clarifying the appropriate management of these patients.
These finding may help explain why some patients with EIB tend to do better once they are treated with ICS. Perhaps there is more of an inflammatory component to EIB than we originally appreciated.
Abstract
Annals of Allergy, Asthma, & Immunology
July 2005 (Volume 95, Number 1)
Asthma Morbidity and Treatment in the Chicago Metropolitan Area: One Decade After National Guidelines
Grant EN, Malone A, Lyttle CS, Weiss KB
Ann Allergy Asthma Immunol. 2005;95:19-25
Although there have been numerous studies investigating the overall asthma morbidity and mortality data for countries as a whole, it is uncommon to see population-based asthma hospitalization and emergency department data for a specific urban area, especially one recognized as having significant morbidity from asthma. These investigators examined the burden of asthma care using a population-based study in the greater Chicago, Illinois, metropolitan area and also attempted to identify demographic and social influences on asthma morbidity and treatment practices.
They conducted a telephone survey of adults in the greater Chicago area between 1999 and 2000 and ended up with 152 adults and children with active asthma. Twenty-five percent of these respondents reported emergency department use and 6.6% required hospitalization in the previous year. Despite these significant healthcare utilization numbers, less than one third reported regular use of asthma controller medications. After the investigators adjusted for age, sex, income, education, and reported current pharmacotherapy, there was a significant race difference in healthcare utilization. Compared with white individuals, African American individuals were 6.3 times more likely to have been treated in the emergency department and over 12 times more likely to have required hospitalization for asthma treatment.
The authors conclude that despite very clear instructions in clinically effective national asthma treatment guidelines such as the National Asthma Education and Prevention Program, poorly controlled asthma remains a significant problem in this metropolitan area (and most likely many others as well). The racial discrepancies in healthcare utilization warrant further study so that factors contributing to this finding can also be further elucidated and addressed.
Abstract
Thorax
June 2005 (Volume 60, Number 6)
Patients With Gastro-oesophageal Reflux Disease and Cough Have Impaired Laryngopharyngeal Mechanosensitivity
Phua SY, McGarvey LP, Ngu MC, Ing AJ
Thorax. 2005;60:488-491
The act of swallowing is a highly sophisticated, complex series of coordinated muscular contractions that move food and secretions from the mouth into the esophagus. If there is a problem somewhere in this orchestrated series of events, then aspiration into the airway may occur. One of the common complications of GERD is chronic cough -- cough that may potentially be caused by several possible mechanisms, including neurologic (ie, vagal) reflexes, laryngeal irritation, or possibly aspiration. Appropriate sensitivity of the laryngopharyngeal structures helps prevent aspiration. If this sensitivity is impaired, then the sensory feedback given by these laryngeal structures used in the act of swallowing could be abnormal.
These authors measured laryngopharyngeal sensitivity (LPS) in 15 patients by using fiber optic endoscopic evaluation of swallowing with sensory testing. This LPS testing is a technique that utilizes the delivery of air pulses to the aryepiglottic folds, eliciting a laryngeal adductor reflex (LAR). LPS is measured by finding the lowest air pressure to elicit the LAR. The study subjects then had either normal saline or 0.1 N hydrochloric acid infused into the laryngopharyngeal area.
They found that the mean LAR threshold was elevated in those with GERD and chronic cough; an elevated threshold indicates decreased sensitivity of the laryngeal structures. Of note, the infusion of hydrochloric acid also elevated the LAR threshold, whereas infusion of saline failed to cause any change in the sensitivity of the laryngopharyngeal area. The authors concluded that chronic exposure of these laryngeal structures to gastric acid may decrease the sensitivity of this anatomic area, with an accompanying increased risk of aspiration.
Abstract
The New England Journal of Medicine
May 19, 2005 (Volume 352, Number 20)
Asthma as a Risk Factor for Invasive Pneumococcal Disease
Talbot TR, Hartert TV, Mitchel E, et al
N Engl J Med. 2005;352:2082-2090
Invasive infection with Streptococcus pneumoniae is more common among people known to be at high risk for severe infection. These patients may include those with a number of medical conditions, including those infected with HIV, as well as those with diabetes mellitus, sickle cell disease, renal disease, hepatic disease (including cirrhosis), chronic obstructive pulmonary disease (COPD), cancer, and immunosuppression due to illness or medications such as chronic corticosteroids, tobacco use, and alcohol abuse. In contrast to the known increase in the risk of invasive pneumococcal disease in patients with COPD, the risk among patients with asthma is not known. Current asthma treatment guidelines do not recommend pneumococcal vaccination as an infection prevention strategy, and current guidelines for pneumococcal vaccination specifically exclude people with asthma. Since approximately 7% to 10% of the US population has asthma, and this percentage appears to be increasing, these authors set out to determine if the incidence of invasive pneumococcal disease was higher in patients with asthma. They conducted a nested, case-control study using data from 2 large, population-based databases. After they analyzed the association, they conducted a cohort analysis to determine the incidence of invasive pneumococcal disease in people with and without asthma who were enrolled in Tennessee's Medicaid program (TennCare).
They matched 10 control patients without invasive pneumococcal disease for every patient with invasive pneumococcal disease, and studied 635 patients and 6350 controls. A total of 114 patients (18%) had asthma. Patients with asthma were nearly 2.5 times more likely to have invasive pneumococcal disease than those without asthma (adjusted odds ratio 2.4; 95% CI 1.9-3.1). The authors concluded that asthma is an independent risk factor for invasive pneumococcal disease, and that the risk among patients with asthma is at least double that of controls. I would assume that these data will most likely be taken into account in future versions of both pneumococcal vaccination and asthma treatment guidelines, with a possible change in the guidelines to suggest the need for pneumococcal vaccination in patients with asthma.
Abstract
April 14, 2005 (Volume 352, Number 15)
Daily Versus As-Needed Corticosteroids for Mild Persistent Asthma
Boushey HA, Sorkness CA, King TS, et al
N Engl J Med. 2005;352:1519-1528
The National Asthma Education and Prevention Program (NAEPP/NIH) Expert Panel Guidelines for the Diagnosis and Management of Asthma divides asthma severity into 4 categories: mild intermittent; and mild, moderate, and severe persistent asthma. Optimal therapy is determined by matching treatment intensity with a patient's asthma severity classification. At the present time, the NAEPP/NIH guidelines recommend regular treatment with an ICS for those patients who have mild persistent asthma. This trial, called the Improving Asthma Control (IMPACT) trial, compared the level of asthma control achieved using regular vs intermittent "as needed" treatment with a controller medication (either an ICS [budesonide] or a leukotriene-receptor antagonist [LTRA, zafirlukast]). The primary outcome measure was morning peak expiratory flow rate (AM PEFR), and secondary outcomes included the frequency of asthma exacerbations, number of days lost from work or school, number of symptom-free days, asthma-related quality of life, and a panel of physiological and biologic measures of asthma activity.
This was a double-blind trial of 225 adults who received an ICS, an LTRA, or placebo. Although rates of exacerbations and AM PEFR were similar among the 3 groups, those treated with daily budesonide had better scores for asthma control, less bronchial hyperreactivity, less exhaled nitric oxide (suggesting less inflammation), greater improvements in prebronchodilator FEV1, less sputum eosinophilia, and more symptom-free days. Those treated with daily zafirlukast did not differ significantly from those treated intermittently. There was not a significant difference among the groups for postbronchodilator scores or quality of life. Patients in the budesonide group reported 26 more days free from symptoms per year compared with the other groups.
This interesting study looks at an important question. Because studies have shown that patients frequently do not comply with asthma medications as instructed, and often do not get into serious trouble with asthma exacerbations, it asks whether we should be looking at intermittent (vs daily) anti-inflammatory therapy in those with mild asthma. Some of the results of the study were somewhat surprising; namely, that the asthma exacerbation rate among the 3 study groups was similar. The other findings, however, including the significant improvements seen in the daily budesonide group, were consistent with what one would expect. This study, which was well structured and conducted, raises some important questions. In my view, however, as well as those of the authors, this should be considered a study to raise the question regarding the appropriateness of intermittent anti-inflammatory treatment for mild persistent asthma. I believe additional studies addressing this question are needed before the treatment guidelines and clinical practice should be changed from their current recommendation of daily anti-inflammatory therapy for mild persistent asthma.
Abstract