Published on January 14, 2008
Pregnant with asthma: Pregnant with asthma 2007/01/05 Supervised by Dr. 楊明智 Reported by Resident孫序東 Introduction: Introduction Definition: Definition Chronic inflammatory disorder with airway hyper- responsiveness and var. airflow obstruction Status asthmaticus Severe obstruction persisting for days or weeks Severe asthma of any type not responding after 30 to 60 minutes of intensive therapy Epidemlology: Epidemlology 7%(William’s) 4~5% of adults and 10% of children(Harrison) Clinical manifestations: Clinical manifestations Classic traid : Wheezing, cough, dyspnea Chest tightness, sputum Chronic with episodic exacerbation Triggers: Triggers Respiratory irritants ( Perfumes, smoke, detergents, strong odors ) Allergens ( pets, carpets, dust mites, pollen ) Infections ( URI, bronchitis, sinusitis ) Drugs ( Morphine, Beta-blockers ) Stress Cold air Exacerbations: Exacerbations Note frequency, severity, duration If required treatment keep airway Physical examination: Physical examination Wheezing and prolonged expiratory phase Presence of nasal polyps, rhinitis, rash allergic component Exacerbationpulsus paradoxus, accessory muscle use Diagnostic studies: Diagnostic studies PFTs peak expiratory flow rate (PEFR)↓ FEV, FEV1/FVC ↓ RV and TLC↑ Allergy suspected serum IgE, eosinophils, skin testing Sputum Curschmann’s spirals ( mucus casts of distal airways) Charcot-Leyden crystals eosinophils Differential diagnosis: Differential diagnosis All that wheezes is not asthma CHF COPD Upper airway obstruction Tumor Laryngeal edema ...etc Slide11: Classification of Severity CLASSIFY SEVERITY Clinical Features Before Treatment Symptoms Nocturnal Symptoms FEV1 or PEF STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Intermittent Continuous Limited physical activity Daily Attacks affect activity > 1 time a week but < 1 time a day < 1 time a week Asymptomatic and normal PEF between attacks Frequent > 1 time week > 2 times a month 2 times a month 60% predicted Variability > 30% 60 - 80% predicted Variability > 30% 80% predicted Variability 20 - 30% 80% predicted Variability < 20% The presence of one feature of severity is sufficient to place patient in that category. Treatment: Treatment Quick relief medications Long-term control medications Quick relief medications: Quick relief medications Short-acting inhaled β2-agonists (1st choice) Akbuterol, pirbuterol, terbutaline Inhaled anticholinergics (ipratropium) improved β2-agonist delivery Systemic corticosteroids Long term control medications: Long term control medications Inhaled or systemic corticosteroids (1st choice) Long acting inhaled β2-agonists (salmeterol) Nedocromil/Cromolyn for young p’t and exercise induced case Theophylline : used in hard to control p’t due to side effect Leukotriene modifiers : By case, especially aspirin-sensitive asthma, may consider trial in all p’t …...禁忌的愛: …...禁忌的愛 Slide16: Stepwise Approach to Asthma Therapy: Adults Step 1: Intermittent Asthma None required Rapid-acting inhaled 2-agonist for symptoms (but < 3-4times/day) Rapid-acting inhaled 2-agonist, cromone, or leukotriene modifier before exercise or exposure to allergen Continuously review medication technique, compliance and environmental control Review treatment every three months. Step up if control is not achieved; step down if control is sustained for at least 3 months Preferred treatments are in bold print Daily Controller Medications Reliever Medications Slide17: Inhaled glucocorticosteroid (< 500 μg BDP or equivalent) Other options (order by cost): sustained-release theophylline, or Cromone, or leukotriene modifier Rapid-acting inhaled 2-agonist for symptoms (but < 3-4 times/day) Other options: inhaled anticholinergic, or short-acting oral 2-agonist, or short-acting theophylline Continuously review medication technique, compliance and environmental control. Review treatment every three months Step up if control is not achieved; Step down if control is sustained for at least 3 months Preferred treatments are in bold print Stepwise Approach to Asthma Therapy: Adults Step 2: Mild Persistent Asthma Daily Controller Medications Reliever Medications Slide18: Inhaled glucocorticosteroid, (200 – 1000 μg BDP or equivalent) plus long-acting inhaled β2agonist Other options (order by cost): Inhaled glucocorticosteroid (500 – 1000 μg BDP equivalent) plus sustained-release theophylline, or Inhaled glucocorticosteroid (500 – 1000 μg BDP equivalent) plus long-acting inhaled β2- agonist, or inhaled glucocorticosteroid at higher doses (> 1000 μg BDP equivalent), or Inhaled glucocorticosteroid (500 – 1000 μg BDP equivalent) plus leukotriene modifier Rapid-acting inhaled 2-agonist for symptoms (but < 3 - 4 times/day) Other options: inhaled anticholinergic or short-acting oral 2-agonist or short-acting theophylline Continuously review medication technique, compliance and environmental control. Review treatment every three months. Step up if control is not achieved; Step down if control is sustained for at least 3 months. Preferred treatments are in bold print. Stepwise Approach to Asthma Therapy: Adults Step 3: Moderate Persistent Asthma Daily Controller Medications Reliever Medications Slide19: Inhaled glucocorticosteroid, (> 1000 μg BDP or equivalent) plus long-acting inhaled β2agonist plus one or more of the following, if needed (order by cost): sustained-release theophylline, or leukotriene modifier or oral glucocorticosteroid Rapid-acting inhaled 2-agonist for symptoms (but < 3-4 times/day) Other options: inhaled anticholinergic or short-acting oral 2-agonist or short-acting theophylline Continuously review medication technique, compliance and environmental control. Review treatment every three months. Step up if control is not achieved; Step down if control is sustained for at least 3 months. Preferred treatments are in bold print. Stepwise Approach to Asthma Therapy: Adults Step 4: Severe Persistent Asthma Daily Controller Medications Reliever Medications Slide20: Part 4: Long-term Asthma Management Stepwise Approach to Asthma Therapy - Adults Reliever: Rapid-acting inhaled β2-agonist prn Controller: Daily inhaled corticosteroid Controller: Daily inhaled corticosteroid Daily long-acting inhaled β2-agonist Controller: Daily inhaled corticosteroid Daily long –acting inhaled β2-agonist plus (if needed) When asthma is controlled, reduce therapy Monitor STEP 1: Intermittent STEP 2: Mild Persistent STEP 3: Moderate Persistent STEP 4: Severe Persistent STEP Down Outcome: Asthma Control Outcome: Best Possible Results Alternative controller and reliever medications may be considered Controller: None -Theophylline-SR -Leukotriene -Long-acting inhaled β2- agonist -Oral corticosteroid Principles of treatment: Principles of treatment Use quick-relief rescue medication for all p’t Persistent asthma requires : Long-term-control medication anti-inflammatory meds preferred Step up treatment if control not maintained Step down if in control Slide22: 是熊貓?是狗狗? Williams obstetrics P1060~1064: Williams obstetrics P1060~1064 Status asthmaticus 0.2% Chromosome 5,6,11,12,14,16,20 Prostaglandins & Ergonovine should be avoided if possible No evidence that pregnancy has a predictable effect on underlying asthma Williams obstetrics P1060~1064: Williams obstetrics P1060~1064 Unless there is severe disease, asthma has relatively minor effects on pregnancy outcome. Slightly increased incidence of preclampsia, preterm labor, low-birth weight infants and perinatal mortality. Status asthmaticus life-threatening Williams obstetrics P1060~1064: Williams obstetrics P1060~1064 Fetal effect Mild No obvious neonatal sequelas Severe Fetal growth restriction Drug : no evidence of harmful FEV1<1L or<20%. Williams obstetrics P1060~1064: Williams obstetrics P1060~1064 Acute asthma : check PaO2>60mmHg SaO2>95% IV use β2-agonists and Steroid Status asthmaticus: Fatigue ,Carbon dioxide retention and Hypoxemia are indications for mechanical ventilation Williams obstetrics P1060~1064: Williams obstetrics P1060~1064 Maintenance medications are continued through delivery Nonhistamine-releasing narcotic agent (ex:fentanyl) maybe preferable Epidural analgesai for labor is ideal 還敢睡~!: 還敢睡~! Slide29: Maternal asthma during pregnancy and fetal outcomes : potential mechanisms and possible solutions Introduction: Introduction There appears to be a circuitous relationship between a mother with asthma and the fetus during pregnancy. The presence of the fetus and placenta may alter maternal immune function and increase asthma severity. An increase in maternal asthma severity can result in a detrimental outcome for the fetus, which includes IUGR, preterm delivery and still birth. IUGR has long-term implications relating to the development of diseases in adult life such as hypertension and diabetes Introduction: Introduction These relationships between the mother with asthma and the fetus also appear to be influenced by the sex of the fetus. The interrelationship between mother and fetus raises questions of how pregnancy can alter asthma severity and what the mechanisms are that contribute to altered fetal growth and survival. Asthma exacerbations during pregnancy: Asthma exacerbations during pregnancy The severity of asthma and the effect of asthma exacerbations during pregnancy on both mother and fetus have been underestimated due to the lack of longitudinal, prospective cohort studies A general dogma of ‘one-third improve, one-third worsen and one third don’t change in their asthma severity during pregnancy’ is a miscalculation There has been a misconception that inhaled glucocorticoid use is harmful to the fetus which results in a lack of compliance with medication use during pregnancy and results in an increased risk of acute exacerbations and poor fetal outcomes Asthma exacerbations during pregnancy: Asthma exacerbations during pregnancy Recent studies indicate that mild or severe exacerbations can affect 55% of women with asthma during pregnancy Exacerbations were associated with self-reported noncompliance with inhaled glucocorticoid treatment, self-reported but unconfirmed presence of a viral infection, cigarette use and seasonal changes during pregnancy A proportion of asthma exacerbations during pregnancy had an unknown cause In these cases it is possible that the cause may simply be the presence of the fetus and placenta and their effect on maternal immune function. Effect of pregnancy on maternal immune function: Effect of pregnancy on maternal immune function Pregnancy maternal immune system maintains immune tolerance to the presence of a genetically different fetus but at the same time continues to function actively against invading pathogens via the innate immune system. The release of placentally derived factors into the maternal circulation has been proposed to redirect the maternal immune system away from cell-mediated immunity and T helper type 1 (Th1) cytokine production to humoral immunity and Th2 cytokine production. Maternal immune changes may upregulate asthma-related mechanisms. Effect of pregnancy on maternal immune function: Effect of pregnancy on maternal immune function Human pregnancy is associated with an increase in maternal blood concentrations of cells of the innate immune system, including monocytes and neutrophils Monocyte cytotoxic function appears to be downregulated during pregnancy by placentally derived factors such as major histocompatibility (MHC) class I chainrelated proteins A and B (MICs) but these cells still mount an inflammatory response via interleukin (IL)-12 production Pregnancy-related neutrophil numbers are increased Both of these cell types are associated with the pathophysiology of asthma and asthma exacerbations Effect of pregnancy on maternal immune function: Effect of pregnancy on maternal immune function Another mechanism that may influence maternal asthma during pregnancy is placental exosomes Exosomes are extracellular vesicles that allow membrane proteins to be secreted into the circulation and have been described to be central in dendritic cell modulation of inflammatory responses by inducing T-cell apoptosis The placental exosomes suppressed T-cell expression of IL-2, CD3-z and JAK-3 proteins Placental exosomes exosomes mediate maternal immune tolerance during pregnancy via FasL-induced inhibition of Th1 cytokine signaling pathways of CD4t T cells This mechanism allows for Th2 predominance in circulating T cells during pregnancy. (Atopic disease) Effect of pregnancy on maternal immune function: Effect of pregnancy on maternal immune function There are a number of circulating proteins that are specific to the presence of maternal asthma and change with gestational age When examining placental and cord blood protein profiles from the same group of women, it was found that there were 14 placental proteins altered in the presence of maternal asthma and 10 proteins altered in cord blood Effect of pregnancy on maternal immune function: Effect of pregnancy on maternal immune function sera of normal pregnancies and pregnancies complicated by asthma induced protein production of the chemokines RANTES, eotaxin and IL-8, the inflammatory cytokine IL-6, and the adhesion factor soluble intercellular adhesion molecule-1 by human bronchial smooth muscle cells in vitro Potentially exacerbating the disease in genetically susceptible individuals. Effect of pregnancy on susceptibility to infection in women with asthma: Effect of pregnancy on susceptibility to infection in women with asthma Women with asthma appear to be more susceptible to respiratory tract infection during pregnancy With an asthma prevalence of 4% reported 50% of respiratory-related hospitalizations of pregnant women had a comorbidity of asthma, suggesting increased susceptibility to respiratory tract infections Pregnant women with asthma also have an increased risk of community-acquired pneumonia There is no scientific information relating to why pregnant women with asthma are more at risk from infection Effect of pregnancy on susceptibility to infection in women with asthma: Effect of pregnancy on susceptibility to infection in women with asthma Combination of asthma and pregnancy-induced immunosuppression may significantly increase the risk of infection and result in acute asthma exacerbations during pregnancy There has been a recent recommendation for vaccination during the influenza season of pregnant, high-risk women, including those with severe asthma Retrospective studies suggest influenza vaccination is safe during the second and third trimesters of pregnancy Effect of fetal sex on maternal asthma: Effect of fetal sex on maternal asthma The sex of the fetus influences maternal asthma severity, with asthma worsening in the presence of a female fetus The most recent study has shown that peak expiratory flow liability was greater in women with asthma pregnant with a female fetus relative to those with a male fetus Clinically, this observation may be of no use It may indicates that fetal sex can influence maternal physiology. Effect of fetal sex on maternal asthma: Effect of fetal sex on maternal asthma Sex-specific factors derived from the fetus that may influence maternal asthma have not been identified Male-derived testosterone, however, was proposed to exert antiinflammatory and bronchodilator effects in the pregnant maternal system, resulting in improved lung function of women with asthma during pregnancy Pregnant with a female fetus there was a significant increase in circulating monocytes and no change in circulating eosinophils These data suggest that worsening asthma in the presence of a female fetus may be mediated by noneosinophilic pathways during pregnancy. Effect of maternal asthma on fetal outcome: Effect of maternal asthma on fetal outcome The mechanisms contributing to altered growth and survival of the fetus appear to be sexually dimorphic In the absence of inhaled steroid use, the female fetus had reduced growth and reduced adrenal function due to decreased placental glucocorticoid metabolism Male neonates had reduced growth and an increased incidence of stillbirth and preterm delivery while the female fetus appeared unaffected Solutions for a healthy outcome: Solutions for a healthy outcome Adverse perinatal outcomes can be avoided with maternal asthma education, joint respiratory and obstetric care and compliance with the use of inhaled glucocorticoids Use of inhaled glucocorticoids to the use of long-acting b2-agonists or anti-immunoglobulin E (IgE) therapies The treatment of severe asthma during pregnancy with salmeterol and fluticasone propionate was associated with reduced neonatal birthweight (The study numbers were small) The Salmeterol Multicentre Asthma Research Trial (SMART) did not provide reassuring evidence for the use of salmeterol, as asthma-related deaths were increased with its use Solutions for a healthy outcome: Solutions for a healthy outcome These findings indicate that inhaled steroid long-acting b2-agonist pharmacotherapy during pregnancy must be used with caution. It has already been reported that this type of care can significantly improve the health of pregnant women with asthma and their offspring Conclusion: Conclusion There are many factors that may influence increased maternal asthma severity during pregnancy, including fetal sex, noncompliance with medication, susceptibility to infection, pregnancy-induced immunosuppression Not all women have worsening asthma during pregnancy, however, and more attention needs to be given to this group of women to understand why their asthma does not change Conclusion: Conclusion Most importantly, prospective cohort studies need to be conducted in the future to examine mechanisms associated with asthma exacerbations and infection during pregnancy, with the goal of developing effective treatment regimes The study of asthma during pregnancy provides an important paradigm for studying fetal and maternal physiology and how each system interacts for an optimal outcome These findings may be applicable to other inflammatory complications during pregnancy, including preeclampsia, connective tissue diseases and inflammatory bowel disease. Thanks for your attentation !: Thanks for your attentation !