The mechanism of cough associated with upper respiratory infection (URI) is poorly understood. This paper reports a study of the role of altered sensitivity of capsaicin-sensitive airway nerves. In a prospective study, baseline (B) capsaicin-induced cough and methacholine-induced airway responsiveness were measured in 103 healthy volunteers. During the following year, 31 subjects reattended for challenge testing during URI (I) and after recovery (R). The log concentration of capsaicin required to elicit two coughs (C2) was significantly lower during infection than recovery but not baseline [median (interquartile range) B = 0.59 (0.28-1.20), I = 0.27 (0-0.89), R = 0.89 (0.28-1.49)]. Log C5 (concentration causing five coughs) was lower during infection than baseline and recovery [B = 1.79 (1.20-2.70), I = 1.49 (0.89-2.08), R = 1.79 (1.20-2.40)]. FEV1 and PC15 methacholine values were unchanged during infection compared to baseline. Subjects with dry cough (n = 14) had lower C5 values during infection than both baseline and recovery, and lower C2 values during infection than recovery; in these subjects, increase in capsaicin sensitivity correlated with cough severity score. Subjects with productive cough or no cough showed no consistent changes during infection. Twenty-six control subjects who reattended without URI showed no change in capsaicin sensitivity. Upper respiratory infection may cause cough as a result of increased sensitivity of capsaicin-sensitive afferent airway nerves without affecting airway calibre or responsiveness.

The mechanism of action of topical intranasal steroids is obscure. To investigate this, we have studied the effects of a topical intranasal corticosteroid, fluticasone propionate on nasal airflow resistance (Rnaw), secretions, cytological smears and symptoms. Fluticasone propionate aqueous nasal spray was given to 11 patients with perennial allergic rhinitis in a double-blind, placebo-controlled study. On each day, patients were challenged with ascending doses of histamine. Rnaw, secretion volume, total protein, mucin, lysozyme and albumin were measured. Nasal smears were taken and sneezes counted. Diary card data were collected for both treatment periods. There was a significant, dose-related increase in Rnaw and sneezing on histamine challenge. A single dose of fluticasone had no effect on any parameter. After 4 weeks of treatment, resistance measurements were reduced (post-challenge g.m.2.8 cmH2O/l/s, Q1-Q3 1.6-4.8; placebo 4.2, 2.9-5.3: P < 0.0001) as were baseline secretion volumes (mean 2.4 ml/5 min, c.i.1.9-3.0; placebo 3.3, 2.8-3.8: P < 0.05). Eosinophil counts were suppressed (fluticasone 5.8%, c.i. 4.0-15.7; placebo 23.3%, 12.4-34.1: P < 0.05) and the composite symptom score reduced (P < 0.05). Fluticasone has long-term effects on the nasal response to histamine in perennial allergic rhinitis and part of this effect is likely to be vascular.

Topical sodium cromoglycate is used to treat allergic diseases of the upper and lower airways. To investigate its mechanisms of action, intranasal histamine challenge was used in nine subjects with perennial allergic rhinitis. After a preliminary day where subjects' reactivity thresholds (D100) for histamine were determined, intranasal sodium cromoglycate was administered in a double-blind, placebo-controlled fashion. Graded (D100/3, D100, D100X3), sequential challenges were performed on days 1 and 21 of each course, and responses measured by changes in nasal airway resistance, sneezes, secretion volume and secretion content: total protein, lysozyme and mucin. After a single dose of sodium cromoglycate, there was no change in resistance, but secretion volumes fell significantly (3.12 ml/5 min c.i. 2.83-3.4; placebo 3.61, c.i. 3.32-3.90: P = 0.026). After a 3-week-course, there was a significant fall in resistance (4.29 cm H2O/l/s, c.i. 3.85-4.72; placebo 5.45, c.i. 5.01-5.88: P < 0.0001). No change in other parameters was observed. Thus, in perennial allergic rhinitis, intranasal sodium cromoglycate has both short- and long-term effects on nasal reactivity to histamine challenge. Acutely, there is a reduction in nasal lavage fluid volume which may be the result of reduced irritant receptor activity. After a 3-week course, there is a reduction in nasal resistance responses, a possible anti-inflammatory effect.

The effects of topical beclomethasone dipropionate on changes in nasal resistance and secretion induced by topical histamine were studied in eight patients with perennial rhinitis. Patients were studied at enrollment, after 3 weeks of beclomethasone (100 micrograms spray to each nasal cavity twice daily), and after 3 weeks of placebo (saline) treatment administered in a double-blind cross-over trial. Nasal airflow resistance (Rnaw) and total protein, albumin, lysozyme and glycoconjugate secretion in nasal lavage fluids were measured after topical application of histamine to the nasal mucosa. Resistance measurements and secretory parameters were similar for the initial study and after placebo treatment. In those studies, histamine (1 and 10 mg) increased both nasal resistance and secretion of total protein, albumin and glycoconjugates. After beclomethasone treatment the rise in respiratory resistance in response to histamine was significantly attenuated (delta Rnaw, +11.57 cm H2O/l/s with placebo, +5.80 with beclomethasone, P < 0.05). Beclomethasone had no effect on histamine-induced secretion. Because nasal resistance is determined mainly by vascular processes, beclomethasone treatment appears to have a prominent action on the vascular bed to reduce mediator-induced vasodilatation in perennial rhinitis.