The Cough Response to Ultrasonically Nebulized Distilled Water in Heart-Lung Transplantation Patients

Abstract

As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using 99mtechnetium diethylene triamine pentaacetate (99mTc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

Cough and ventilatory adjustments evoked by aerosolised capsaicin and distilled water (fog) in man

“…Although there is no dispute that mechanical and chemical stimuli applied to the larynx also cause cough, we believe that the reflex responses observed in this study are mainly due to activation of sensors located below the laryngeal level. In facts, a considerable amount of information points at the possibility that, in both animals and humans, the sensory endings mediating laryngeal cough are not promptly activated by agents such as fog and inhaled citric acid (Higenbottam et al, 1989;Forsberg et al, 1990;Stockwell et al, 1993;Tatar et al, 1996;Fontana et al, 1999b). This may be particularly true with threshold concentrations of irritants.…”

“…Fontana). debate (Widdicombe, 2001). Animal experiments performed in vivo have revealed that RARs and C-fibre sensory receptors may be activated by both non-isotonic water solutions and capsaicin, albeit to different extents (Pisarri et al, 1991(Pisarri et al, , 1992Mohammed et al, 1993;Morikawa et al, 1997), and many inhalation studies have confirmed the powerful tussigenic action of these agents in normal subjects and in patients with respiratory and nonrespiratory disorders (Higenbottam et al, 1989;Fontana et al, 1997Fontana et al, , 1998Fontana et al, , 1999aDavenport et al, 2002;Kastelik et al, 2002;Dicpinigaitis, 2004). A peculiar type of low-threshold mechanoreceptors innervated by myelinated vagal fibres has been described recently in the guinea pig extrapulmonary airways (Canning et al, 2004;Mazzone, 2005;Mazzone et al, 2005).…”

A noninvasive electromyographic study on threshold and intensity of cough in humans

“…They include citric acid, capsaicin, histamine, bradykinin and prostaglandins [1][2][3][4][5], as well as ultrasonically nebulized distilled water (UNDW) and solutions low in permeant anion content [1,[6][7][8][9][10][11]. One of the most valuable indices of a subject's susceptibility to cough stimuli may be represented by the cough threshold [8][9][10], which has been employed in studies aimed at evaluating the separate role of osmolarity and ion content of inhaled water solutions both in normal subjects and asthmatic patients [8,9].…”

“…During UNDW or low-chloride challenges, cough response has frequently been assessed in terms of cough frequency, i.e. the number of expiratory thrusts during the inhalation period [6,7,11]. This method, however, treats all coughs as equal and does not allow a quantitative evaluation of the intensity of the cough motor response in terms of strength of expiratory muscle contraction and, hence, of force or pressure generated by them.…”

Gastro-oesophageal reflux disease and non-asthma lung disease

“…It has been increasingly recognised that GERD, present in 48-76% of patients post-transplantation [13][14][15], may be a key factor in the development and progression of BOS [80]. Factors predisposing to GERD-related lung disease in this population include gastroparesis [81], vagus nerve dysfunction, a high incidence of post-operative oropharyngeal dysphagia [82], and depressed cough reflex due to the lack of innervation of the allograft [83]. Most lung transplant patients with GERD lack classic symptoms [14], and although acid suppression therapy is frequently given to this patient group, non-acid reflux is present in up to 50% as documented by the finding of bile acids in lung lavage samples [13], a finding associated with BOS in one study [84].…”