Nocturnal asthma and timing of treatment

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      Nocturnal deterioration of pulmonary function in asthmatic patients is a well-recognized and well-documented phenomenon. The mechanism of this “morning dip,” however, remains uncertain. Although the circadian rhythms of body temperature, corticosteroid, catecholamine, histamine, and opiate peptide levels, and even sleep itself have been shown to be in phase with the diurnal variation in asthma, a causal relationship has yet to be established. Increased nighttime bronchial reactivity to histamine, acetylcholine, and house dust allergen have been demonstrated. In general, continuous treatment with theophylline, beta-adrenergic agonists, or corticosteroids attenuates the degree of morning dip but does not completely eliminate the circadian rhythm of asthma. The significance of nocturnal asthma is emphasized by the observation that asthma deaths occur more frequently during nighttime hours and are often preceded by large daily swings in peak expiratory flow. Further studies examining the etiology and treatment of nocturnal asthma are needed.
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        • Hetzel MR
        • Clark TJH
        • Houston K
        Physiological patterns in early morning asthma.
        Thorax. 1977; 32: 418-423
        • Hetzel MR
        • Clark TJH
        Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate.
        Thorax. 1980; 35: 738-782
        • Connolly CK
        The effect of bronchodilators on diurnal rhythms in airway obstruction.
        Br J Dis Chest. 1981; 75: 197-203
        • Dawkins KD
        • Muers MF
        Diurnal variation in airflow obstruction in chronic bronchitis.
        Thorax. 1981; 36: 618-621
        • Mak H
        • Chipps BE
        • Menkes HA
        • et al.
        Diurnal variation of air and helium-oxygen flow-volume curves in asthmatic children.
        Br J Dis Chest. 1982; 76: 51-56
        • Bateman JRM
        • Pavia D
        • Clarke SW
        Mucociliary clearance during sleep in healthy subjects.
        Thorax. 1977; 32 (abstr): 644
        • Hetzel MR
        • Clark TJH
        • Branthwaite MA
        Asthma: analysis of sudden deaths and ventilatory arrests in hospital.
        Br Med J. 1977; 1: 808-811
        • Cochrane GM
        • Clark TJH
        A survey of asthma mortality in patients between ages 35 and 64 in the Greater London hospitals in 1971.
        Thorax. 1975; 30: 300-305
        • Bateman JRM
        • Clark SW
        Sudden death in asthma.
        Thorax. 1979; 34: 40-44
        • Clark TJH
        • Hetzel MR
        Diurnal variation of asthma.
        Br J Dis Chest. 1977; 71: 87-92
        • Gervais P
        • Reinberg A
        • Gervais C
        • Smolensky M
        • Defrance O
        Twenty-four-hour rhythm in the bronchial hyperreactivity to house dust in asthmatics.
        J Allergy Clin Immunol. 1977; 59: 207-213
        • Davies RJ
        • Green M
        • Schofield N
        Recurrent nocturnal asthma after exposure to grain dust.
        Am Rev Respir Dis. 1976; 114: 1011-1019
        • Cartier MD
        • Malo JL
        • Forest F
        • et al.
        Occupational asthma in snow crab-processing workers.
        J Allergy Clin Immunol. 1984; 74: 261-269
        • Kales A
        • Beall GN
        • Balor GF
        • Jacobson A
        • Kales JD
        Sleep studies in asthmatic adults: relationship of attacks to sleep stage and time of night.
        J Allergy. 1968; 41: 164-173
        • Shapiro C
        • Montgomery I
        • Catterall JR
        Breathing, bronchoconstriction, and sleep stage in nocturnal asthma.
        Thorax. 1982; 37 (abstr): 238
        • Hetzel MR
        • Clark TJH
        Does sleep cause nocturnal asthma?.
        Thorax. 1979; 34: 749-754
        • Dees SC
        The role of gastroesophageal reflux in nocturnal asthma in children.
        NC Med J. 1974; 35: 230-233
        • Martin ME
        • Grunstein MM
        • Larsen GL
        The relationship of gastroesophageal reflux to nocturnal wheezing in children with asthma.
        Ann Allergy. 1982; 49: 318-322
        • Spaulding HS
        • Mansfield LE
        • Stein MR
        • Sellner JC
        • Gremillion DE
        Further investigation of the association between gastroesophageal reflux and bronchoconstriction.
        J Allergy Clin Immunol. 1982; 69: 516-521
        • Rachelefsky G
        • Berquist W
        • Rowshan N
        • Welch M
        • Katz R
        • Siegel S
        Gastroesophageal reflux (GER) in asthmatic children compared to normals.
        J Allergy Clin Immunol. 1982; 69 (abstr): 143
        • Chen WY
        • Chai H
        Airway cooling and nocturnal asthma.
        Chest. 1982; 81: 675-680
        • DeVries K
        • Goei JT
        • Booy-Noord H
        • Orie NGM
        Changes during 24 hours in the long function and histamine hyperreactivity of the bronchial tree in asthmatic and bronchitis patients.
        Int Arch Allergy. 1962; 20: 93-101
        • Rachiele A
        • Malo JL
        • Cartier A
        • Pineau L
        • Ghezzo M
        • Martin RR
        Circadian variations of airway response to histamine in asthmatic subjects.
        Bull Eur Physiopath Respir. 1983; 19: 465-469
        • Scott PH
        • Tabchnik E
        • MacLeod S
        • Correia J
        • Newth C
        • Levison H
        Sustained-release theophylline for childhood asthma: evidence for circadian variation of theophylline pharmacokinetics.
        J Pediatr. 1981; 99: 476-479
        • Lesko LJ
        • Brousseau D
        • Canada AT
        • Eastwood G
        Temporal variations in trough serum theophylline concentrations at steady state.
        J Pharm Sci. 1980; 69: 358-359
        • Coulthard KP
        • Birkett DJ
        • Lines DR
        • Grgurinovich N
        • Grygiel JJ
        Bioavailability and diurnal variation in absorption of sustained release theophylline in asthmatic children.
        Eur J Clin Pharmacol. 1983; 25: 667-672
        • Barnes PJ
        • Greening AP
        • Neville L
        • Timmers J
        • Poole GW
        Single-dose slow-release aminophylline at night prevents nocturnal asthma.
        Lancet. 1982; I: 299-301
        • Davies PDO
        • Fennerty AG
        • Benfield GFA
        • Parrish RW
        • Campbell IA
        Twice daily slow release theophylline vs. placebo for “morning-dipping” in asthma.
        Br J Clin Pharmacol. 1984; 17: 335-340
        • Fairfax AJ
        • McNabb WR
        • Davies HJ
        • Spiro SG
        Slow-release oral salbutamol and aminophylline in nocturnal asthma: relation of overnight changes in lung function and plasma drug levels.
        Thorax. 1980; 35: 526-530
        • Horn CR
        • Clark TJH
        • Cochrane GM
        Inhaled therapy reduces morning dips in asthma.
        Lancet. 1984; II: 1143-1145
        • Barnes PJ
        • Fitzgerald GA
        • Dollery CT
        Circadian variation in adrenergic responses in asthmatic subjects.
        Clin Sci. 1982; 62: 349-354
        • Carpentieve G
        • Marino S
        • Castello F
        Effects of inhaled fenoterol on the circadian rhythm of expiratory flow in allergic bronchial asthma.
        Chest. 1983; 83: 211-214
        • Reinberg A
        • Gervas P
        • Choussade M
        • Fraboulet G
        • Duburque B
        Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma.
        J Allergy Clin Immunol. 1983; 71: 425-433
        • McAllister WAC
        • Mitchell DM
        • Collins JV
        Prednisolone pharmacokinetics compared between night and day in asthmatic and normal subjects.
        Br J Clin Pharmacol. 1981; 11: 303-304