Angelo Petroianni

Comorbidity, Hospitalization, and Mortality in COPD: Results from a Longitudinal Study

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV1, RV, PaO2, and PaCO2 were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV1, PaO2, the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.

Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis

Background: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. Objectives: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. Methods: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. Results: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 ± 6 vs. 19.5 ± 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO2/FiO2 as compared with spontaneous breathing (group A: 148.5 ± 52 vs. 99 ± 39, p = 0.0004; group B: 134 ± 36 vs. 89 ± 26, p = 0.0004). NIV reduced the respiratory rate (26 ± 7 vs. 36 ± 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2–6 months). Conclusions: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches.

Assessment of right ventricular function by strain rate imaging in chronic obstructive pulmonary disease

The purpose of the current study was to compare right ventricular (RV) myocardial wall velocities (tissue Doppler imaging) and strain rate imaging (SRI) parameters with conventional echocardiographic indices evaluating RV function in chronic obstructive pulmonary disease (COPD) patients. In total, 39 patients with COPD and 22 healthy subjects were included in the current study. Seventeen patients had pulmonary artery pressure <35 mmHg (group I) and 22 patients had pulmonary artery pressure >35 mmHg (group II). Tissue Doppler imaging, strain and strain rate (SR) values were obtained from RV free wall (FW) and interventricular septum. Respiratory function tests were performed (forced expiratory volume in one second/vital capacity (FEV1/VC) and carbon monoxide diffusion lung capacity per unit of alveolar volume (DL,CO/VA)). Strain/SR values were reduced in all segments of group II patients compared with group I patients and controls with lowest values at basal FW site. A significant relationship was shown between peak systolic SR at basal FW site and radionuclide RV ejection fraction. A significant relationship was shown between peak systolic SR at basal FW site and DL,CO/VA and FEV1/VC. In conclusion, in chronic obstructive pulmonary disease patients, strain rate imaging parameters can determine right ventricular dysfunction that is complementary to conventional echocardiographic indices and is correlated with pulmonary hypertension and respiratory function tests.

Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD.

AIM To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD. METHODS In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 microg once-daily (8 am); Tr2: TIO 18 microg (8 am) + FOR 12 microg (8 pm); Tr3: FOR 12 microg twice-daily (8 am and 8 pm); Tr4: TIO 18 microg (8 am) + FOR 12 microg twice-daily (8 am and 8 pm); Tr5: FOR 12 microg twice-daily (8 am and 8 pm) + TIO 18 microg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV(1) (DeltaFEV(1)) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol. RESULTS Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of DeltaFEV(1) were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die). CONCLUSIONS In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV(1) during the 24 h (CV=0.256). These results are relevant for opening new ways in clinical practice.

Maximal respiratory static pressures in patients with different stages of COPD severity

BackgroundIn this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values.Subject and methods110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe.ResultsBoth MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1.ConclusionThe measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.

Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation

Background Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Methods Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Results Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Effect of insulin on airway responsiveness in patients with type 2 diabetes mellitus: a cohort study.

Background. The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus. Methods. We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV1)% from baseline (Δ FEV1) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR). Results. A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 ± 7 years and the mean duration of disease was 13.5 ± 7.7 years. The mean decrease of FEV1 at pre-insulin assessment was 2.96 ± 2.6%. Compared with the pre-insulin value, a significant increase of Δ FEV1 was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Δ FEV1, 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively). Conclusions. The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.

Clarithromycin and pulmonary infiltration with eosinophilia

Pulmonary diseases induced by drugs include bronchial asthma, pulmonary infiltration with eosinophilia, diffuse fibrosing alveolitis, vasculitis, and pleural diseases.1–4 Most such diseases recede when the drug is withdrawn, although on rare occasions the pulmonary damage is irreversible and progressive.4 5 We describe a patient with asthma referred to our respiratory diseases clinic who twice developed fever and pulmonary infiltration with eosinophilia after taking antibiotics. A 17 year old white man who has had bronchial asthma since childhood was referred to our clinic in January 2002. The patient also reported sinusitis and allergic rhinitis. Results of earlier prick tests and radioallergosorbent tests were positive for wall pellitory ( Parietaria judaica ) and grasses, and the tests resulted in a mild increase in peripheral blood eosinophil counts (0.6-0.7 × 109/l (6-7%)). His general practitioner had prescribed salbutamol as a rescue treatment. The patient did not report any allergy to drugs. In December 2001 he had reported fever (38°C), accompanied by mucopurulent nasal secretion and pain in his forehead. X ray pictures of the paranasal sinuses showed maxillary sinusitis on the right side and hypertrophy of the turbinates. The general practitioner prescribed combined amoxicillin (875 mg) and clavulanic acid (125 mg) twice daily for seven days, followed by clarithromycin (500 mg) twice daily for a further seven days. Figure 1 shows the patients course of treatment. At the end of this treatment period the patient reported dry cough and mild dyspnoea. Chest x ray pictures showed pulmonary consolidations localised at the right apex. Fig 1 Temporal relation between the patients course of treatment and pulmonary infiltration …

Herpes simplex pneumonia: Combination therapy with oral acyclovir and aerosolized ribavirin in an immunocompetent patient

BACKGROUND Herpes simplex viruses (HSVs) are known to cause respiratory tract infections in immunocompromised hosts and, in rare instances, in immunocompetent hosts. Numerous in vitro and in vivo studies have shown that aerosolized administration of ribavirin can potently and selectively inhibit viral replication in pulmonary disease, thereby increasing the effectiveness of acyclovir in HSV. OBJECTIVE In this case study, we reported on a 46-year-old immunocompetent woman with HSV type 1 pneumonia with bilateral pulmonary infiltrates but without mucocutaneous lesions. METHODS The diagnosis was confirmed using cytology, viral culture, and serology. Because of the persistence of fever and dyspnea, we chose an antiviral therapy. The patient received oral acyclovir and aerosolized ribavirin to improve the antiviral effectiveness of the acyclovir and to reduce the symptoms and the time to resolution of the pulmonary disease. RESULTS After 3 days of therapy, dyspnea and fever decreased and hypoxemia improved. After 2 weeks, computed tomography showed complete resolution of pulmonary abnormalities. The patient did not report any adverse effects. CONCLUSIONS In our case study, we demonstrated that therapy with a combination of aerosolized ribavirin and oral acyclovir may be useful to reduce the severity of viral infection, the adverse effects, and the days of hospitalization. To our knowledge, this is the first report in the literature of the synergistic effects of the combination of aerosolized ribavirin and oral acyclovir in the treatment of an immunocompetent patient with HSV pneumonia.

Effect of Postural Variations on Carbon Monoxide Diffusing Capacity in Healthy Subjects and Patients with Chronic Obstructive Pulmonary Disease

Background: The scientific literature does not supply enough information about the effects of postural changes on diffusing lung capacity for carbon monoxide (DLCO) in patients with chronic obstructive pulmonary disease (COPD), in particular regarding the prone position. Objectives: We evaluated posture-related changes in DLCO in healthy subjects and in COPD patients in order to especially assess how prone posture affects gas exchange. Methods: In this cross-sectional study, DLCO was measured in 10 healthy subjects and 30 COPD patients in standing, seated, supine and prone positions. Results: In healthy individuals, DLCO tended to improve from the upright to the supine position (21.42 ± 2.90 and 26.07 ± 5.11 ml/min/mm Hg, respectively); in the same group, changing the position from upright to prone also caused significant improvements in DLCO (absolute value, 21.42 ± 2.90 vs. 24.80 ± 4.39 ml/min/mm Hg, p < 0.05, or percent of predicted, 78.58 ± 11.12 vs. 91.44 ± 13.23, p < 0.05) and in DLCO proportional to alveolar volume (DLCO/VA; 4.52 ± 0.57 vs. 5.66 ± 1.48 ml/min/mm Hg/l, p < 0.05). No significant differences in DLCO have been observed in COPD patients from the standing to the prone position. Multivariate linear regression models showed that the posture-related changes in DLCO, DLCO expressed as percent of predicted and in DLCO/VA are directly correlated with the transition from upright/sitting to supine/prone. Conclusions: In healthy subjects, the effect of postural changes on DLCO could be explained by a more homogeneous perfusion, whereas the lack of variations in COPD patients could be attributed to the increased rigidity of lung capillaries, which could represent an early sensitive marker of damage of the alveolar capillary interface in these patients.