Stefano Carlone

Atrial Natriuretic Peptide, Renin and Aldosterone in Obstructive Lung Disease and Heart Failure

Elevations of atrial natriuretic peptide (ANP) in congestive heart failure (CHF) and chronic obstructive lung disease (COLD) are presumably due to atrial hypertension, while secondary hyperaldosteronism in these patients is thought to result from diminished renal perfusion. The responsiveness of the ANP and renin (PRA)-aldosterone (PA) systems to acute increases in right atrial pressure has not been studied in these patients, but in normals a reciprocal relationship between ANP with PRA and PA has been shown. The authors monitored venous pressure (VP, reflective of right atrial pressure), ANP, PRA and PA in 15 stable COLD patients, seven stable CHF patients and three normal controls at baseline and after elevation of VP by antishock trousers. Inflation of the trousers resulted in increased VP and ANP (p less than 0.05): control ANP, 84 +/- 17 to 108 +/- 23 pg/ml; COLD ANP, 176 +/- 5 to 200 +/- 7; and CHF ANP, 388 +/- 20 to 499 +/- 37. PRA and PA were not suppressed by increasing ANP levels and the delta ANP/delta VP ratio was similar among groups. No intergroup differences in resting PRA and PA were noted, but PRA was higher (p = 0.007) and PA tended to be higher (p = 0.08) in a sub-group of six edematous patients, as compared with non-edematous patients and controls. These findings: (1) confirm previously reported ANP differences between COLD and CHF; (2) indicate that the ANP system remains responsive to physiologic manipulations in COLD and CHF; and (3) demonstrate that ANP and the PRA-PA axis are not reciprocally related in either group.

INDACO project: a pilot study on incidence of comorbidities in COPD patients referred to pneumology units

BackgroundChronic Obstructive Pulmonary Disease (COPD) is often associated with comorbidities, especially cardiovascular, that have a heavy burden in terms of hospitalization and mortality. Since no conclusive data exist on the prevalence and type of comorbidities in COPD patients in Italy, we planned the INDACO observational pilot study to evaluate the impact of comorbidities in patients referred to the outpatient wards of four major hospitals in Rome.MethodsFor each patient we recorded anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI).ResultsHere we report and discuss the results of the first 169 patients (124 males, mean age 74±8 years). The prevalence of patients with comorbidities was 94.1% (25.2% of cases presented only one comorbidity, 28.3% two, 46.5% three or more). There was a high prevalence of arterial hypertension (52.1%), metabolic syndrome (20.7%), cancers (13.6%) and diabetes (11.2%) in the whole study group, and of anxiety-depression syndrome in females (13%). Exacerbation frequency was positively correlated with dyspnea score and negatively with BMI. Use of combination of bronchodilators and inhaled corticosteroids was more frequent in younger patients with more severe airways obstruction and lower CCI.ConclusionsThese preliminary results show a high prevalence of comorbidities in COPD patients attending four great hospitals in Rome, but they need to be confirmed by further investigations in a larger patients cohort.

Health and social impacts of COPD and the problem of under-diagnosis

This article deals with the prevalence and the possible reasons of COPD underestimation in the population and gives suggestions on how to overcome the obstacles and make the correct diagnosis in order to provide the patients with the appropriate therapy. COPD is diagnosed in later or very advanced stages. In Italy the rate of COPD under-diagnosis ranges between 25 and 50% and, as a consequence, the patient does not consult his doctor until the symptoms have worsened, mainly due to exacerbations. A missed diagnosis influences the timing of therapeutic intervention, thus contributing to the evolution into more severe stages of the illness. An incisive intervention to limit under-diagnosis cannot act only in remittance (passive diagnosis), but must be the promoter for a series of preventive actions: primary, secondary and rehabilitative. To reduce under-diagnosis, some actions need to be taken, such as screening programs for smokers subjects, use of questionnaires aimed to qualify and monitor the disease severity, spirometry, early diagnosis. There is a consensus regarding diagnoses based on screening of at-risk subjects and symptoms, rather than screening of the general population. In practice, all individuals over 40 years of age with risk factors should make a spirometry test. Screening actions on a national scale can be the following: compilation of questionnaires in waiting rooms of doctor’s offices or performing simple maneuvers to evaluate the expiratory force at pharmacies. It is now widely recognized that COPD is a complex syndrome with several pulmonary and extrapulmonary components; as a result, the airway obstruction as assessed by FEV1 by itself does not adequately describe the complexity of the disease and FEV1 cannot be used alone for the optimal diagnosis, assessment, and management of the disease. The identification and subsequent grouping of key elements of the COPD syndrome into clinically meaningful and useful subgroups (phenotypes) can guide therapy more effectively. In conclusion, we firmly believe that an early and correct diagnosis can influence positively the progress of the disease (lowering the lung function impairment), decrease the risk of exacerbations, relieve symptoms and increase the patients’ quality of life leading also to a decrease in costs associated to the exacerbations and hospitalization of the patient.

Red Blood Cell Alkalosis and Decreased Oxyhemoglobin Affinity

The behavior of the oxyhemoglobin curve was studied in ten patients with respiratory alkalosis (arterial [H+] ≤ 37 nM, pCO2 ≤ 32 mmHg and HCO−3 ≤ 22.0 mEq/L) and ten patients with metabolic alkalosis ([H+] ≤ 34 nM, pCO2 ≥ 37 mmHg and HCO−3 ≥ 28.0 mEq/L) to determine whether different alkalotic states similarly affect the red blood cell [H+] and 2,3-diphosphoglycerate interaction and thus the oxygen affinity of hemoglobin. The findings were statistically indistinguishable in respiratory alkalosis and metabolic alkalosis: a) low plasma [H+], normal red blood cell [H+], and high transmembrane [H+] gradient; b) elevated red blood cell 2,3-diphosphoglycerate inversely proportional to low arterial plasma [H+]; c) decrease in oxygen affinity of hemoglobin when normalized for plasma [H+], but less decreased when normalized for red blood cell [H+]. Other factors capable of affecting the oxygen affinity of hemoglobin were: mean corpuscular hemoglobin concentration; red blood cell adenosine triphosphate; carboxyhemoglobin; and methemoglobin were not significantly different between groups. These results: 1) agree with data previously reported from this laboratory on patients with portal-systemic encephalopathy; 2) underscore the importance of RBC [H+] in defining the oxygen affinity of hemoglobin; 3) suggest the decrease in oxygen affinity of hemoglobin is mediated through the 2,3-diphosphoglycerate elevation; and 4) indicate the high transmembrane [H+] gradient is principally due to the cellular accumulation of [H+] (2,3-diphosphoglycerate ionization). [Am J Med Sci 1982; 284(2):8–16.]

COPD management as a model for all chronic respiratory conditions: report of the 4 th Consensus Conference in Respiratory Medicine

BackgroundNon-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions.MethodsThese issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3–4 November 2016.Results and conclusionsRegarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.