A 28 year old man presents with cough, shortness of breath & wheezing. The symptoms started when he was running initially. Now the symptoms are present while walking or even at rest. During childhood he suffered from atopic dermatitis. His father and sister also suffered from atopic dermatitis. He also has hay fever from 14 years of age. The cause of bronchospasm

Answer: c) Type I hypersensitivity (HARRISON 19TH ED, P-1669; ROBBINS 9TH ED, P-679)ASTHMAHall marks of the diseaseIncreased airway responsivenessEpisodic bronchoconstrictionInflammation and hyperplasia of the bronchial wallsIncreased mucous secretion Atopic asthmaMost common typeClassic example of IgE-mediated (type I) hypersensitivity reactionUsually begins in childhoodPositive family history and skin test positiveCommonly suffer from other atopic diseases, particularly allergic rhinitis, which may be found in over 80% of asthmatic patients, and atopic dermatitis (eczema)Exaggerated TH2 and IgE response to environmental allergens (dusts, pollen, animal dander, animal foods) in genetically predisposed individualsThe TH2 cytokines IL-4, IL-5, and IL13 are important mediatorsDiagnosed by allergen sensitization by serum radio-allergosorbent tests (RAST)Non-Atopic asthmaNo evidence of allergen sensitization; No family history; Negative skin testsTriggered by viral respiratory infectionsRhinovirus, parainfluenza and RSV are the most common organisms(not bacteria)Drug induced asthmaAspirin sensitive asthma in patients with recurrent rhinitis and nasal polypsExercise-induced bronchoconstriction:Begins during exercise or within 3 minutes after its end.Peaks within 10-15 minutes.Resolves by 60 minutes.This phenomenon is thought to be a consequence of the airways' attempt to warm and humidify an increased volume of expired air during exercise.Cardiac asthma - wheezing precipitated by decompensated heart failure.Catamenial asthma - Women may experience at predictable times during the menstrual cycle.MorphologyThe most striking finding - occlusion of bronchi & bronchioles by thick, tenacious mucous plugsHistologically the mucous plugs contains whorls of shed epithelium "Curschmann spirals"Sputum contains Charcot-Leyden crystalsEpithelial cells present in the sputum - Creola bodies Clinical featuresWheezing, breathlessness, chest tightness and cough particularly at night or early morningSeverity of asthma exacerbationsFeatureMildModerateSevereImminent respiratory arrestBreathlessnessWhile walkingAt rest, limits activityAt rest, interferes with conversationAt rest, muteTalks inSentencesPhrasesWordsSilentRespiratory rateIncreasedIncreased> 30/min> 30/minUse of accessory muscles; suprasternal retractionsAbsentCommonlyUsuallyParadoxical thoracoabdominal MovementWheezeEnd expiratoryThroughout expirationThroughout inspiration and expirationAbsentPulse/min<100100 -120>120BradycardiaPulsus paradoxusAbsent <10 mm HgMay be present 10- 25 mm HgOften present >25 mm HgAbsence suggests respiratory muscle fatiguePEF or FEV1 % predicted or % personal best> 70%40-69%<40%< 25%PaO2 (on air, mm Hg)Normal>60<60<60PCO2 (mm Hg)< 42 mm Hg<42 mm Hg>42 mm Hg>42 mm HgSaO2 (on air)>95%90-95 %< 90 %<90%1 kPa = 7.5 mmHgClassification of asthma severityFeatureIntermittentPersistentMildModerateSevereSymptoms< 2 days/week> 2 days/weekDailyThroughout dayNight awakenings< 2/month3 - 4/month> 1/week but not dailyDailyShort-acting B2-agonist use for symptom control< 2 days/week> 2 days/week, but not dailyDailySeveral times per dayInterference with normal activityNoneMinor limitationSome limitationExtreme limitationFEV1Normal between Exacerbations > 80% predicted> 80% predicted60 - 80%< 60%FEV1 /FVCNormalNormal5% reduced> 5% reducedLife-threatening acute severe asthma - featuresPEF < 33 % predicted (< 100 L/min)SpO2 < 92% or PaO2 < 60 mmHgNormal or raised PaCO2Silent chestCyanosisFeeble respiratory effortBradycardia or arrhythmiasHypotensionExhaustionConfusionComaDiagnosis of asthma: Compatible clinical history + any one of the following>15% (and 200 mL)increase in FEV1 following administration of bronchodilator or corticosteroids (Positive bronchodilator response - strongly confirms the diagnosis of asthma)>20% diurnal variation on > 3 days in a week for 2 weeks on Peak expiratory flow (PEF) meter diaryFEV1 > 15% decrease after 6 minutes of exercise Note:Bronchial provocation testing with inhaled histamine or methacholine may be useful when asthma is suspected but spirometry is non-diagnostic.Bronchial provocation is not recommended if the FEV1 is less than 65% of predicted.A positive methacholine test is defined as a > 20% fall in the FEV1 at exposure to a concentration of 8 mg/mL or less.A negative test has a negative predictive value for asthma of 95%.Asthma managementSeveritySymptoms and SignsInitial PEF (or FEY1)Clinical CourseMildDyspnea only with activityPEF > 70% predicted or personal best* Usually cared for at home* Prompt relief with inhaled SABA* Possible short course of oral systemic corticosteroidsModerateDyspnea interferes with or limits usual activityPEF 40-69% predicted or personal best* Usually requires office or ED visit* Relief from frequent inhaled SABA* Oral systemic corticosteroids; some symptoms last for 1-2 days after treatment is begunSevereDyspnea at rest; interferes with conversationPEF < 40% predicted or personal best* Usually requires ED visit and likely hospitalization* Partial relief from frequent inhaled SABA* Oral systemic corticosteroids; some symptoms last for > 3 days after treatment is begun* Adjunctive therapies are helpfulSubset: Life- threateningToo dyspneic to speak; perspiringPEF < 25% predicted or personal best* Requires ED/hospitalization; possible ICU* Minimal or no relief from frequent inhaled SABA* Intravenous corticosteroids* Adjunctive therapies are helpfulED, emergency department; FEV1, forced expiratory volume in 1 second; ICU, intensive care unit; PEF; peak expiratory flow; SABA, short acting b2-agonist.Oral corticosteroids should generally be prescribed for early administration at home in patients with moderate to severe asthmaExcept for the respiratory rate of 35/min, the patient given in the question has moderate asthma (pulse rate- 120/min, BP-110/70 mmHg, Oxygen saturation of 90% (most important) and peak expiratory flow less than 50%)STEP WISE MANAGEMENT OF BRONCHIAL ASTHMAStep 1Step 2Step 3Step 4Step 5MildintermittentMildpersistentModerate persistentSevere persistentVery severe persistentSABA when neededRegular SABA + low dose ICS(200ug)Add LABA* Benefit present, but inadequate control- continue LABA & | ICS dose (800mg)* No response: stop LABA & | ICS dose (800mg/day)* | ICS dose upto (2000mg/day)* Addition of fourth drug: leukotriene receptor antagonist, SR theophylline, b2- agonist tablet* Use daily steroid tablet* High dose ICS (2000ug/day)* Refer for specialist careICS -inhaled corticosteroid; LABA - inhaled long acting beta-2-agonist; LTRA-leukotriene receptor antagonist; SABA - inhaled short acting beta-2-agonist; OCS - oral corticosteroidsNAEPP 3 recommendations emphasize daily anti-inflammatory therapy with inhaled corticosteroids as the cornerstone of treatment of persistent asthma.