Last 3 months of life in home-ventilated patients: the family perception.

We studied the family's perception of care in patients under home mechanical ventilation during the last 3 months of life. In 11 respiratory units, we submitted a 35-item questionnaire to relatives of 168 deceased patients exploring six domains: symptoms, awareness of disease, family burden, dying, medical and technical problems. Response rate was 98.8%. The majority of patients complained respiratory symptoms and were aware of the severity and prognosis of the disease. Family burden was high especially in relation to money need. During hospitalisation, 74.4% of patients were admitted to the intensive care unit (ICU). 78 patients died at home, 70 patients in a medical ward and 20 in ICU. 27% of patients received resuscitation manoeuvres. Hospitalisations and family economical burden were unrelated to diagnosis and mechanical ventilation. Families of the patients did not report major technical problems on the use of ventilators. In comparison with mechanical invasively ventilated patients, noninvasively ventilated patients were more aware of prognosis, used more respiratory drugs, changed ventilation time more frequently and died less frequently when under mechanical ventilation. We have presented good points and bad points regarding end-of-life care in home mechanically ventilated patients. Noninvasive ventilation use and diagnosis have impact on this burden.

Oral nifedipine in chronic cor pulmonale secondary to severe chronic obstructive pulmonary disease (COPD).

Hemodynamic effects of orally-administered nifedipine were evaluated in 12 patients with pulmonary hypertension secondary to severe COPD after short-term (30 and 60 minutes) treatment and then again in eight of these 12 patients after long-term (average 55 days) treatment. Pulmonary vascular resistance (PVR) decreased from 426 +/- 52 to 294 +/- 28 dynes.s.cm-5 (p less than 0.001) after therapy with 20 mg sublingual nifedipine (at 60 minutes). Cardiac index (CI) increased from 3.7 +/- 0.2 to 4.6 +/- 0.3 L/min/m2 (p less than 0.001). There was a decrease in mean pulmonary artery pressure (MPAP) only in 4/12 patients after Nifedipine. There was no significant fall in PaO2, while PvO2 and oxygen delivery (CI X CaO2) increased significantly 60 minutes after administration of sublingual nifedipine. PVR decreased from 482 +/- 82 to 374 +/- 44 dynes.s.cm-5 (p less than 0.05) after long-term nifedipine therapy. The changes in PVR and CI 60 minutes after administration of nifedipine in the patients on long-term treatment were similar to those observed with the same doses of nifedipine before initiation of therapy. Despite beneficial hemodynamic effects in two of eight patients, there was progressive clinical worsening. The benefit of long-term administration of nifedipine is difficult to predict on the basis of short-term effects.

Sleep-related breathing impairment in myotonic dystrophy.

Respiratory failure has been described in myotonic dystrophy; it worsens during sleep but its central or peripheral origin has yet to be determined. Moreover, patients may present severely disturbed sleep and daytime somnolence. Eight patients with mild to moderate myotonic dystrophy were studied to assess breathing function while awake and during sleep by means of the pulmonary function tests, nocturnal polysomnographic examination and the multiple sleep latency test (MSLT). Three patients had restrictive respiratory defects; none had signs of airway obstruction. All patients had very disrupted nocturnal sleep. Of six patients who underwent the MSLT only two showed a mild tendency to sleep during the day. Six patients had pathological apnoea plus hypopnoea index [(A+H)I] and there was a prevalence of central apnoeas. The apnoeas occurred while resting but awake and throughout all sleep stages. Only two patients (the ones with the least vital capacity) had episodes of progressive oxygen desaturation during rapid eye movement sleep, similar to those found in other restrictive disorders and in chronic obstructive pulmonary disease. It is concluded that the breathing pattern characteristic of our myotonic dystrophy patients was the occurrence of central apnoeas both at rest while awake and during sleep.

Outcome of COPD patients performing nocturnal non-invasive mechanical ventilation.

The role of non-invasive nocturnal domiciliary ventilation (NNV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnia is still discussed. The aims of this study were to evaluate the long-term survival, the clinical effectiveness and side-effects of NNV in these patients. Forty-nine stable hypercapnic COPD patients on long-term oxygen therapy (LTOT) were assigned to two groups: in Group 1, 28 patients performed NNV by pressure support modality in addition to LTOT; in Group 2, 21 patients continued their usual LTOT regimen. Treatment was assigned according to the compliance to NNV, after an in hospital period. Mortality rate, hospital stay (HS) and ICU admissions (IA) were recorded in the two groups. HS and IA were compared to those recorded in a similar period of follow-back. Lung and respiratory muscle function, dyspnoea, and exercise capacity (by 6-min walk test) were evaluated baseline and every 3-6 months up to 3 yr. Mean follow-up time was 35 +/- 7 months. Mortality rate was not different between the two groups: 16, 33, 46% and 13, 28, 50% at 1, 2 and 3 yr in Groups 1 and 2 respectively. Lung and respiratory muscle function did not significantly change over time. A significant increase in 6-min walk test (from 245 +/- 78 to 250 +/- 88, 291 +/- 75, 284 +/- 89 m after 1, 2 and 3 yr respectively, P < 0.01) was observed only in patients undergoing NNV. In comparison to the follow back HS significantly decreased in both groups (from 37 +/- 29 to 15 +/- 12 and from 32 +/- 18 to 17 +/- 11 days/pt/yr in Groups 1 and 2 respectively, P < 0.001) whereas IA significantly decreased only in patients performing also NNV (from 1.0 +/- 0.7 to 0.2 +/- 0.3/pt/yr, P < 0.0001). Addition of NNV by pressure support modality to LTOT does not improve long term survival but significantly reduces ICU admissions and improves exercise capacity in severe COPD with hypercapnia.

Failure of automatic control of ventilation (Ondine's curse) associated with viral encephalitis of the brainstem: a clinicopathologic study of one case.

A case of Ondine's curse associated with hypothalamic dysfunction in an 8-year-old boy is described. The neuropathological examination revealed a viral encephalitis affecting the hypothalamus and the brainstem. In the medulla the inflammatory process involved the reticular formation and the nuclei considered to control automatic respiration such as the dorsal motor nucleus of the vagus, the nucleus tractus solitarii and the nucleus ambiguous. Although Ondine's curse following viral infection of the central nervous system has been previously reported this represents the first case of viral encephalitis to be pathologically documentated.

Antibodies to topoisomerase II in idiopathic pulmonary fibrosis.

Antibodies to DNA topoisomerase II (anti-topoisomerase II) were detected by ELISA in the sera of 18 out of 41 (44%) patients with idiopathic pulmonary fibrosis (IPF). Follow-up sera were also obtained from 19 of the patients. DNA topoisomerase II binding remained constantly high or low in the majority of follow-up sera, but 2 out of the 8 positive cases became negative while 3 out of the 11 negative cases became positive during follow-up. No association was found between occurrence of anti-topoisomerase II antibodies and any indices of disease severity. Furthermore, individual patient follow-up did not show any correlation between changes in topoisomerase II binding and deterioration or improvement of clinical status. In conclusion our study shows that although anti-topoisomerase II are detectable in a large fraction (approximately 50%) of IPF patients and are useful for diagnostic purposes, they do not provide a measure of clinical activity.

Cefepime versus ceftazidime in the treatment of lower respiratory tract infections.

The objective of the study was to compare the safety and efficacy of cefepime and ceftazidime in the treatment of community acquired lower respiratory tract infections of moderate intensity. Eighty-six patients were randomized at a 2:1 ratio to receive respectively cefepime 1 g b.i.d. or ceftazidime 1 g t.i.d. The drugs were well tolerated and the occurrence of adverse events in each group was comparable. The rates of satisfactory clinical response were 96% (49/51) for cefepime and 89% (24/27) for ceftazidime. A total of 73 pathogens were isolated and pathogen eradication rates were 98% and 96% respectively for the cefepime and ceftazidime treatment groups. In conclusion, the data confirmed that cefepime could be a good alternative to ceftazidime.

Acute respiratory failure, due to severe obstructive sleep apnoea syndrome, managed with nasal positive pressure ventilation.

The complications of endotracheal intubation are particularly frequent in patients with obstructive sleep apnoea syndrome (OSAS). We prospectively tested nasal ventilation in such patients admitted for acute respiratory failure. Six consecutive patients, aged 17-70 yrs, were selected for the study. All patients were confused or severely obtunded, Glasgow Coma Score (GCS) 10 (SD 2). With nasal bi-level positive airways pressure (BiPAP) all these patients improved clinical status and arterial blood gas values, avoiding intubation and invasive mechanical ventilation. The median pH increased from 7.26 (SD 0.06) to 7.36 (0.01) and to 7.43 (0.02) after, 1-3 and 24 h of nasal ventilation, respectively. Nasal ventilation lasted an average of 21 (3) h on the first day. All patients were discharged home after a median hospital stay of 28 (11) days.

End-of-life decision-making in respiratory intermediate care units: a European survey.

A survey was performed on behalf of the European Respiratory Society to assess end-of-life practices in patients admitted to European respiratory intermediate care units and high dependency units over a 6-month period. A 33-item questionnaire was sent by e-mail to physicians throughout Europe and the response rate was 28 (29.5%) out of 95. A total of 6,008 patients were admitted and an end-of-life decision was taken in 1,292 (21.5%). The mortality rate in these patients was 68% (884 out of 1,292). The patients received similar proportions of withholding of treatment (298 (23%) out of 1292), do-not-resuscitate or do-not-intubate orders (442 (34%) out of 1,292) and noninvasive mechanical ventilation as the ceiling of ventilatory care (402 (31%) out of 1,292). Withdrawal of therapy was employed in 149 (11%) out of 1,292 patients and euthanasia in one. Do-not-intubate/do-not-resuscitate orders were more frequently used in North compared with South Europe. All of the 473 competent patients directly participated in the decision, whereas, in 722 (56%) out of 1,292 cases, decision-making was reported to be shared with the nurses. In European respiratory intermediate care units and high dependency units, an end-of-life decision is taken for 21.5% of patients admitted. Withholding of treatment, do-not-intubate/do-not-resuscitate orders and noninvasive mechanical ventilation as the ventilatory care ceiling are the most common procedures. Competent patients are often involved, together with nurses.

Parasympathetic activity assessed by diving reflex and by airway response to methacholine in bronchial asthma and rhinitis.

It has been suggested that airway hyperreactivity in asthma is associated with increased parasympathetic tone. We have accordingly assessed parasympathetic responsiveness in five groups of subjects (17 normal controls, 8 patients with extrinsic rhinitis, 6 with intrinsic rhinitis, 10 extrinsic asthmatic patients, 7 intrinsic asthmatic patients) by examining their responses to both diving reflex and methacholine inhalation challenge. The mean fall in heart rate during the diving test was significantly greater in asthmatic subjects than in normal controls and in patients with rhinitis. The diving-induced bradycardia was significantly greater in intrinsic than in extrinsic asthmatic subjects. There was a good correlation between the drop in heart rate during diving test and the provocation dose of methacholine producing a 45% decrease in specific airway conductance both in patients with rhinitis and in asthmatic patients. There was a less good correlation between diving response and clinical severity score in the same asthmatic patients. These results indicate that intrinsic asthma is associated with a marked degree of cholinergic hyperreactivity. The diving test seems to provide an accurate method for the analysis of the parasympathetic system in asthma.

Effects of beta-agonists on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease.

In a single-blind placebo-controlled trial in 12 patients with advanced chronic obstructive pulmonary disease (COPD) we compared the effects of nebulized salbutamol (1 mg), clenbuterol (30 micrograms) and placebo (4 ml of normal saline) on spirometric indices (FVC, FEV1), maximal expiratory flows (Vmax50 and Vmax25), the distance walked in 6 min (6MD), assessment of breathlessness by visual analogue scale (VAS), and estimates by the patients of perceived exertion (RPE). Both clenbuterol and salbutamol produced significant increases in FEV1, FVC, Vmax50 and Vmax25. With both drugs, 6MD increased significantly (p less than 0.01) and breathlessness decreased significantly without an appreciable increase in RPE after exercise despite the extra distance covered. The absolute improvements in FEV1 and 6MD after clenbuterol were correlated (r = 0.763, p less than 0.01), but these indices were not correlated after salbutamol (r = 0.121, p greater than 0.1). The lack of correlation between the changes in 6MD and FEV1 after salbutamol might indicate that relief of airways obstruction is not the only explanation for the effects on distance walked, at least with salbutamol.

Effects of nifedipine and oxygen on pulmonary haemodynamics in severe scoliosis.

In the present study the response of the pulmonary circulation to a vasodilator agent (nifedipine) and to low-flow oxygen (FiO2 35%) has been studied both at rest and during exercise (steady state, 25 W) in nine patients with severe scoliosis (spinal curve + 100 degrees, FVC 38%). All patients were dyspneic on exertion and had had at least one episode of right heart failure. The mean pulmonary artery pressure (Pap) ranged from 13 to 37 mmHg at rest and ranged from 30 to 75 mmHg during exercise. Standard exercise, performed 60 min after 20 mg sublingual nifedipine, was associated with a reduction in mean Pap (49 mmHg) as compared with exercise performed during the control period (58 mmHg, p less than 0.001). Pulmonary vascular resistance (PVR) on exercise decreased more on nifedipine (28.9%) than on oxygen (13.9%) (p less than 0.05). Our results suggest that nifedipine improves pulmonary haemodynamics in patients with severe scoliosis complicated by cor pulmonale.

Pulmonary vascular responsiveness at rest and during exercise in idiopathic pulmonary fibrosis: effects of oxygen and nifedipine.

To detect whether pulmonary vascular responsiveness is a factor which can aggravate the pulmonary hypertension induced by irreversible pulmonary fibrosis, we examined the acute hemodynamic effects of low-flow oxygen and of nifedipine both at rest and during exercise in 8 patients with idiopathic pulmonary fibrosis (IPF). During exercise, the increments in pulmonary artery pressure, pulmonary vascular resistance (PVR), and right ventricular stroke work index relative to resting values were blunted by both treatments. During exercise, both systemic vascular resistance and PVR decreased more significantly after nifedipine than on oxygen (p less than 0.001). At exercise, nifedipine administration induced a greater increment in oxygen delivery (CaO2 X CI) than that produced by oxygen breathing (p less than 0.01). Our results in patients with IPF seem to confirm that active vasoconstriction of pulmonary vessels may contribute to the pulmonary hypertension during exercise. The evaluation of reversibility of pulmonary hypertension by nifedipine in IPF deserves further long-term studies.

[The correlation between radiological and haemodynamic pictures in the diagnosis of pulmonary hypertension in chronic obstructive diseases (author's transl)]. / Correlazioni radiologico-emodinamiche nella diagnosi di ipertensione arteriosa polmonare in pazienti pneumopatici cronici.

A comparison between the radiographical findings and the haemodynamic data was made in 53 cases of chronic bronchial obstruction. The results were used in an assessment of the reliability of standard chest X-rays in the diagnosis of pulmonary hypertension. Reference is also made to quantitative indices. Several cases are presented by way of example.

[Chronic eosinophilic pneumonia (author's transl)]. / La polmonite cronica eosinofila.

The clinical and radiologic findings of the chronic eosinophilic pneumonia are presented. A personal observation of one case is reported. This should be the first in the Italian roentgenologic literature. The importance of radiology in the diagnosis and in the evolution of the disease is stressed.

[Radiologic evaluation of bronchial asthma (author's transl)]. / Il bilancio radiologico nell'asma bronchiale.

The physiopathologic and anatomic findings of bronchial asthma are shortly reviewed. A description follows of the radiologic patterns based on personal experience. Only seldom the radiologic investigations provide the possibility to reach the correct diagnosis of bronchial asthma. But they always complete the clinical evaluation and allow the demonstration of the numerous and frequent complications which influence the evolution and prognosis of the disease.

[The assessment of pulmonary arterial pressure by pulsed Doppler in patients with obstructive pneumopathy]. / Valutazione della pressione arteriosa polmonare mediante Doppler pulsato nei pazienti affetti da pneumopatia ostruttiva.

The severity of pulmonary arterial hypertension can be assessed by duplex-Doppler echocardiography, a subxiphoid approach and a general-purpose duplex device. Normally, the peak Doppler flow velocity occurs in midsystole and the flow profile is parabolic (bullet-like). In pulmonary arterial hypertension, changes in vascular compliance cause maximal acceleration of blood in early systole, with shortening of pulmonary acceleration time (AcT, or time to peak velocity). In the more severe cases, a midsystolic notching is visible, related to rapid deceleration of blood flow, followed by a brief secondary increase in velocity in the late systole. We studied 19 adult patients with chronic obstructive pulmonary disease with duplex-Doppler examination, with a subxiphoid approach and right heart catheterization. The study was diagnostic in all cases with Doppler recordings of good quality. An relationship was found between AcT and pulmonary mean or systolic arterial pressure at rest. An evident accurate prediction of pulmonary arterial pressure in emphysematous patients is possible by means of pulsed Doppler, also in case of low-level hypertension. We believe this method to be a simple and reliable adjunct to the non-invasive work-up of emphysematous patients and to represent a good alternative to the classical parasternal approach, which is often not feasible in these patients.

Respiratory flutter during carbon dioxide rebreathing in patients with obstructive sleep apnea syndrome.

In order to detect the dysfunction of the upper airway muscles in awake patients with obstructive sleep apnea syndrome (OSAS), we examined the effect of a chemical stimulus (CO2) on flow-volume loops obtained during tidal breathing. Six flow-volume curves during forced maneuvers and six flow-volume tracings during rebreathing of CO2 were recorded in 20 patients with OSAS. All patients had numerous obstructive apneas (mean apnea index 61 +/- SD 33, percentage of obstructive apneas 76 +/- 29) associated with moderate to severe degrees of arterial oxygen desaturation. Of the 18 patients in whom at least six flow-volume loops could be obtained during CO2 rebreathing, 13 exhibited respiratory flutter (range: grade 1 to 6) during tidal breathing in the flow-volume tracing (RF VtCO2). The greater the degree of RF VtCO2 during wakefulness, the less was the lowest oxygen saturation (LSaO2) during sleep. In fact, all four patients with RF VtCO2 score 6 had LSaO2 below 30%.

[Heart arrhythmias in chronic respiratory failure due to chronic obstructive bronchopneumopathy: the incidence and correlations with nocturnal respiratory disorders]. / Aritmie cardiache nella insufficienza respiratoria cronica da broncopneumopatia cronica ostruttiva: incidenza e correlazioni con le turbe respiratorie notturne.

The aim of this study was to assess: frequency and type of cardiac arrhythmias in patients with severe stable chronic obstructive lung disease (COLD) and chronic respiratory failure (CRF); diurnal or nocturnal predominance of the detected arrhythmias; prospective relationships between arrhythmias and nocturnal hypoxemic-hypercapnic episodes. All patients were examined with careful and complete medical history, chest roentgenogram, standard electrocardiogram, mono and bidimensional echocardiogram, respiratory function tests, arterial blood gases at rest, 24-hour dynamic electrocardiographic recording and, simultaneously, transcutaneous nocturnal monitoring of respiratory gases (TCNM). We studied 14 men: all complained of exercise-induced dyspnoea for 8 +/- 6 years; 10 of them reported usual nocturnal snoring. Respiratory function tests provided the following values (expressed in percentage compared with theoretical ones): vital capacity 58.6 +/- 15, forced expiratory volume/s 36 +/- 19, Tiffeneau index 60 +/- 19, Motley index 160 +/- 35, carbon monoxide diffusion capacity 48 +/- 26. Arterial blood gas analysis at rest resulted: PO2 47 +/- 4.5 mmHg, PCO2 49 +/- 7.9 mmHg, pH 7.38 +/- 0.3. Right ventricular diameter obtained with mono and bidimensional echocardiogram was 32 +/- 4.6 mm. Right pulmonary descending artery measured on chest roentgenogram was 23 +/- 3.8 mm. Nocturnal transcutaneous monitoring of respiratory gases showed mean PO2 of 40 +/- 9.7 mmHg and mean PCO2 of 75 +/- 19 mmHg. During night-time maximum percentage reductions of PO2 (36 +/- 17%) were measured.(ABSTRACT TRUNCATED AT 250 WORDS)