Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold).

Cough is among the symptoms most commonly associated with an acute, viral upper respiratory tract infection (URI), such as the common cold. Two previous studies incorporating capsaicin cough challenge methodology have demonstrated that cough reflex sensitivity is transiently enhanced during URI. These studies used single measurements of cough reflex sensitivity during the URI period. To our knowledge, no previous studies have included multiple measurements of cough reflex sensitivity to capsaicin during a URI to evaluate the stability of this measure during the acute viral illness. In the current methodological investigation, we performed capsaicin cough challenges in 42 subjects with URI who were otherwise healthy, adult, nonsmokers (25 female). Subjects were enrolled within 72 h of onset of illness and randomly assigned to 3 groups (n = 14 each) that underwent cough reflex sensitivity measurement (C2 and C5) at days 0 and 1 for group 1; days 2 and 3 for group 2; or days 4 and 5 for group 3. Each subject returned 4-8 weeks post-viral infection to establish a healthy baseline measurement (recovery). Our results support that cough reflex sensitivity to capsaicin, as measured by C5, is a sensitive measure that remains stable during 6 days of a URI. These results suggest that cough reflex sensitivity measures in the presence of a URI provide a sensitive and reproducible approach that could be used in future investigations seeking to test experimental antitussive therapies.

Unusual synchronous lung tumors: mucoepidermoid carcinoma and mucinous adenocarcinoma.

Primary mucoepidermoid tumors of the lung are rare entities. Synchronous primary malignancies of the lung involving mucoepidermoid carcinoma and mucinous adenocarcinoma are even rarer and constitute a unique set of patient population. The presentation, diagnosis and treatment strategies for this patient population are not well described. In most cases, the diagnosis of synchronous primary lung malignancy is made after pathological examination of the resected lung specimen. Molecular and genetic analysis is now being used to supplement the diagnosis of synchronous primary lung malignancies. In this work, we briefly discuss the current state of knowledge of this unique combination of primary lung malignancies and describe the clinical presentation and management of a patient with a rare combination of synchronous primary lung malignancies.

Effect of viral upper respiratory tract infection on the urge-to-cough sensation.

BACKGROUND: Recently, interest has emerged in the sensation of irritation that precedes the motor act of coughing; this phenomenon has been termed the urge-to-cough (UTC). Although one previous study has demonstrated a transient enhancement of cough reflex sensitivity during acute upper respiratory tract infection (URI), the effect of URI on UTC has not previously been investigated. METHODS: Employing standard cough challenge methodology, we measured cough reflex sensitivity in 24 otherwise healthy adult nonsmokers during URI and again after recovery (4-8 weeks later) by determining C(2) and C(5), the concentrations of capsaicin inducing 2 or more and 5 or more coughs, respectively. In addition, we determined the capsaicin concentration at which the UTC sensation first occurred, without an associated motor cough, and termed it C(u). Furthermore, we determined the difference between concentrations of capsaicin inducing the first motor event of cough (C(1)) and C(u), and have termed it C(Δ). RESULTS: During URI, cough reflex sensitivity as measured by C(1) (p = 0.033) and C(5) (p = 0.001), as well as the urge-to-cough threshold, C(u) (p = 0.046), were significantly enhanced compared to the post-recovery state. The degree of change in cough reflex sensitivity (C(5)) was significantly greater than that of the urge-to-cough threshold, C(u) (p = 0.044). CONCLUSION: Our results demonstrate that the UTC sensation is transiently enhanced during URI. We also confirm the results of the lone previous study that demonstrated transient enhancement of cough reflex sensitivity during URI. The UTC threshold may represent an additional relevant end point to measure in future studies evaluating potential antitussive agents.

M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. I. Normal rat bladder.

The muscarinic receptor subtype-activated signal transduction mechanisms mediating rat urinary bladder contraction are incompletely understood. M(3) mediates normal rat bladder contractions; however, the M(2) receptor subtype has a more dominant role in contractions of the hypertrophied bladder. Normal bladder muscle strips were exposed to inhibitors of enzymes thought to be involved in signal transduction in vitro followed by a single cumulative concentration-response curve to the muscarinic receptor agonist carbachol. The outcome measures were the maximal contraction, the potency of carbachol, and the affinity of the M(3) -selective antimuscarinic agent darifenacin for inhibition of contraction. Inhibition of phosphoinositide-specific phospholipase C (PI-PLC) with 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH(3)) reduces carbachol potency and reduces darifenacin affinity, whereas inhibition of phosphatidyl choline-specific phospholipase C (PC-PLC) with O-tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt (D609) attenuates the carbachol maximal contraction. Inhibition of rho kinase with (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride (Y-27632) reduces carbachol potency and increases darifenacin affinity. Inhibition of rho kinase, protein kinase A (PKA), and protein kinase G (PKG) with 1-(5-isoquinolinesulfonyl)-homopiperazine.HCl (HA-1077) reduces the carbachol maximal contraction, carbachol potency, and darifenacin affinity. Inhibition of protein kinase C (PKC) with chelerythrine increases darifenacin affinity, whereas inhibition of rho kinase, PKA, PKG, and PKC with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine.2HCl (H7) reduces the carbachol maximum and carbachol potency while increasing darifenacin affinity. Inhibition of rho kinase, PKA, and PKG with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl (H89) reduces carbachol maximum and carbachol potency. Both the M(2) and the M(3) receptor subtype are involved in normal rat bladder contractions. The M(3)subtype seems to mediate contraction by activation of PI-PLC, PC-PLC, and PKA, whereas the M(2) signal transduction cascade may include activation of rho kinase, PKC, and an additional contractile signal transduction mechanism independent of rho kinase or PKC.