First Exploration of the Altered Microbial Gut-Lung Axis in the Pathogenesis of Human Refractory Chronic Cough.

PURPOSE: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM). METHODS: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances. RESULTS: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC. CONCLUSION: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication.

M4 muscarinic receptors mediate acetylcholine-induced suppressant effects on the cough reflex in the caudal nucleus tractus solitarii of the rabbit.

It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control mechanism of the cough reflex. Thus, identification of the involved mAChR subtypes could be of considerable interest for novel therapeutic strategies. In pentobarbital sodium-anesthetized, spontaneously breathing rabbits we investigated the contribution of different mAChR subtypes in the modulation of mechanically and chemically induced cough reflex. Bilateral microinjections of 1 mM muscarine into the cNTS increased respiratory frequency and decreased expiratory activity even to complete suppression. Interestingly, muscarine induced strong cough-suppressant effects up to the complete abolition of the reflex. Microinjections of specific mAChR subtype antagonists (M1-M5) into the cNTS were performed. Only microinjections of the M4 antagonist tropicamide (1 mM) prevented muscarine-induced changes in both respiratory activity and cough reflex. The results are discussed in light of the notion that cough involves the activation of the nociceptive system. They also suggest that M4 receptor agonists may have an important role in cough downregulation within the cNTS.

Somatic points for cough and urge to cough in chronic coughers.

In patients with chronic cough and age-matched control subjects, we attempted to evoke coughing and/or an urge to cough (UTC) by finger pressure along the sternocleidomastoid and sternum, on the lower cervical or first dorsal vertebrae, the jugular notch as well as with maximum neck extension and flexion These mechanical actions were ineffective in controls but reproducibly evoked coughing or UTC in about 50% of chronic coughers; sternal and spinal responses were abolished temporarily by local cooling. The results may disclose a novel paradigm of cough sensitisation possibly involving central convergence of somatic and visceral neural stimuli.

Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD.

Proceedings of the European Seminars in Respiratory Medicine course, Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD, held in Taormina, Italy, on 3-4 March, 2017.

A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough.

BACKGROUND: Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO2 rebreathing test in patients with chronic cough of any origin. METHODS: Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO2 for 5 min. Fractional end-tidal CO2 (Fetco2) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed. RESULTS: At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P < .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern. CONCLUSIONS: The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. TRIAL REGISTRY: European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/.

Optimising Inhaled Pharmacotherapy for Elderly Patients with Chronic Obstructive Pulmonary Disease: The Importance of Delivery Devices.

Chronic obstructive pulmonary disease (COPD) is common in older people. Inhaled medications are the mainstay of pharmacological treatment of COPD, and are typically administered by handheld inhalers, such as pressurised metered-dose inhalers and dry powder inhalers, or by nebulisers. For each of the three major categories of aerosol delivery devices, several new inhalers have recently been launched, each with their own particularities, advantages and disadvantages. Consequently, broader availability of new drug-device combinations will increase prescription opportunities. Despite this, however, there is limited guidance available in published guidelines on the choice of inhalers, and still less consideration is given to elderly patients with COPD. The aim of this article is to provide a guide for healthcare professionals on device selection and factors to be considered for effective inhaled drug delivery in elderly COPD patients, including device factors (device type and complexity of use), patient factors (inspiratory capabilities, manual dexterity and hand strength, cognitive ability, co-morbidities) and considerations for healthcare professionals (proper education of patients in device use).

Effect of an anti-reflux medical device in the control of deflation cough: A placebo-controlled comparative study with an antacid drug in chronic coughers.

BACKGROUND: Deflation cough (DC), i.e. the cough-like expiratory expulsive efforts evoked by maximal lung emptying, is partially inhibited by prior intake of an antacid. We wished to compare the effects of an anti-reflux medical device (Gastrotuss(®)) and of a widely used antacid drug (Maalox(®)) on the number of expiratory thrusts evoked by maximal lung emptying in chronic cough patients. METHODS: Twenty consecutive chronic cough outpatients also presenting DC attended the clinic on three separate occasions and were requested to inhale to near total lung capacity and then exhale maximally for at least 6 s. Trained investigators detected aurally the number of cough efforts evoked by maximal lung emptying prior to and 1, 5, 10, 30 e 60 min after administration of either Maalox(®), or Gastrotuss(®) or placebo. The liking of the administered agents was also rated. RESULTS: In control conditions, maximal lung emptying was consistently accompanied by the appearance of DC. The number of efforts was unchanged after placebo whereas it was markedly (P < 0.001) reduced 1-10 min following Maalox(®) and Gastrotuss(®) administration. The value of liking for Gastrotuss(®) was greater (P < 0.01) than those of Maalox(®) and placebo. CONCLUSIONS: Pre-treatment with anti-reflux agents with a substantially different composition are equally effective in inhibiting DC. The liking of the two compounds used in the present experiments differed considerably and may be important to improve adherence to treatment in patients undergoing long-term therapy for reflux-related symptoms.

Providing transcultural to children and parents: an exploratory study from Italy.

PURPOSE: Immigration and multiculturalism are relatively recent in Italian society, and social adaptation to this new reality is still ongoing. Immigrants to Italy mainly come from China, Albania, Northern Africa, and Eastern Europe. Because no study about this topic was found, our goal was to investigate attitudes and problems encountered by Italian nurses in a paediatric setting with regard to nursing care of children and their families from other countries. DESIGN AND METHODS: Exploratory study. An anonymous 11-item "ad hoc" questionnaire was distributed to 201 ward nurses of the Meyer Paediatric Hospital, Florence, Italy in May 2007. FINDINGS: In all, 129 nurses (64.1%) answered the questionnaire; 78.3% reported having experienced some difficulties in providing care to foreign children and their families. The language barrier was reported as the most important, although more than two-thirds of nurses speak a language in addition to Italian. About half of the nurses encountered problems in care because of different nutrition and personal hygiene customs of patients and their families. Religious and spiritual practices were perceived as a problem by only a minority of nurses. Almost half of the nurses reported having been involved in care situations wherein they felt embarrassed or disapproval concerning the behaviour of parents of foreign children. This included discomfort about different views concerning the social role of women. Nurses also perceived in foreign parents opinions different from their own about the role of nurses (10%) and attitudes of children toward pain associated with medical procedures (45%). CONCLUSIONS: This is the first study we know about regarding attitudes of Italian nurses toward multicultural care. Effective communication is the main aspect of delivering culturally competent care. Language as a means of communication is paramount for an effective nurse-patient relationship without which nursing care is unsatisfactory. Our study indicates the importance of teaching transcultural nursing, cultural diversity, and culturally competent nursing care in university and continuing professional education programs for Italian nurses and nursing students. CLINICAL RELEVANCE: This study indicates the strengths and weaknesses of Italian nurses in managing the care of non-Italian children and their families; and the need for a background of transcultural nursing and theory.

Incidence of cystic fibrosis in the Albanian population.

BACKGROUND: Cystic fibrosis (CF) is the most common life-threatening genetic disease in the Western world. Its incidence varies between 1:4,000 and 1:2,500 among Europeans. No data are available on the incidence of CF among Albanians, mainly due to difficulties of the local health system. GOALS: To estimate the incidence of CF and the prevalence of healthy carrier status among Albanian ethnic people; to evaluate the incidence of hypertrypsinaemia at birth among Albanian newborns. METHODS: We used the database of the newborn screening of Tuscany, Italy for the period 1991-2005. Children born to both Albanian parents in Tuscany were identified and incidences were calculated. RESULTS: The incidence of CF among Albanians (1/555, 99% CI: 1/2,980-1/306) was significantly higher than the rest of the Tuscan population (1/4,101, 99% CI: 1/5,564-1/3,248). The prevalence of CF carrier status among Albanians living in Tuscany is estimated to be 1/12 (99%CI 1/27-1/9) while in the rest of the Tuscan population it is 1/32 (99%CI 1/37-1/28). The incidence of hypertrypsinaemia at birth among Albanian newborns (1/55 99%CI: 1/74-1/44) was significantly higher than in the rest of the population (1/84, 99%CI 1/88-1/82). CONCLUSION: The incidence of CF among Albanians is considerably higher than expected. Albanian people have a risk to give birth to children with CF higher than the rest of Europeans. The implementation of a newborn screening program in Albania, together with a CF follow up program is highly advisable.

Patient risk of contact with respiratory pathogens from inanimate surfaces in a cystic fibrosis outpatient clinic. A prospective study over a four-year period.

Acquisition of respiratory pathogens such as Pseudomonas aeruginosa (PA) is associated with increased morbidity and mortality in cystic fibrosis (CF). Research on the prevalence of these pathogens on environmental surfaces of a CF Center is scanty, and so far no study has determined what risk CF patients have of coming in contact with them during their visits to the CF Center. This study is aimed at assessing the prevalence of some respiratory pathogens in samples taken systematically during a 4-year period from inanimate surfaces and sinks in a CF Outpatient Clinic, and to estimate the risk that a non-PA colonized CF patient has of contact with PA when visiting the CF Center. Microbiological samples were taken and cultured from the inanimate surfaces and sinks of the Outpatient clinic of a CF Center once a month from 2001 to 2005. Four hundred and sixty environmental specimens were collected: 36.3% were positive for respiratory pathogens (23% of rooms' inert surfaces, 49.5% of sinks). Achromobacter xylosoxidans was found in 0.8% of surface samples. PA was isolated in 22.8% samples. The estimated risk for each non-colonized patient of coming in contact with PA on the surfaces in the Clinic at each visit was 5.4 per thousand (CI95% 0.9-30.1). Genotyping of a sample of environmental PA strains revealed a genetic relation between environmental and clinical isolates in most cases. Micro-organisms relevant for CF patients can be found on inanimate surfaces of a CF Center, although the risk for patients of coming in contact with PA during their visits to the CF center seems low.