Effect of CPAP-therapy on bronchial and nasal inflammation in patients affected by obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper and lower airways inflammation. Continuous positive airway pressure (CPAP) is the elective treatment of OSAS. The aim of the present study was to assess the effect of CPAP-therapy on airway and nasal inflammation. METHODS: In 13 non-smoking subjects affected by untreated OSAS and in 11 non-smoking normal volunteers, airway inflammation was detected by analyses of the induced sputum. In the OSAS group measurements were repeated after 1, 10 and 60 days of the appropriate CPAP treatment. In addition, in 12 subjects of the OSAS group, nasal inflammation was detected by the analysis of induced nasal secretions at baseline, and after 1, 10 and 60 days of CPAP treatment. RESULTS: OSAS patients, compared to normal controls, showed at baseline a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum. One, 10 and 60 days of appropriate CPAP-therapy did not change the cellular profile of the induced sputum. In addition, in the OSAS patients, the high neutrophilic nasal inflammation present under baseline conditions was not significantly modified by CPAP-therapy. Finally, no patients developed airway hyper-responsiveness after CPAP therapy. CONCLUSIONS: In OSAS subjects, the appropriate CPAP-therapy, while correcting the oxygen desaturation, does not modify the bronchial and nasal inflammatory profile.

Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA. METHODS: We enrolled 18 obese patients with OSA (10 men, age 48.2 +/- 8.4 years), 15 obese patients without OSA (eight men, age 52.8 +/- 11 years) and 10 healthy subjects (five men, age 42 +/- 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry. RESULTS: Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 +/- 2.1 and 17.9 +/- 2.1 p.p.b.) than in healthy subjects (7.2 +/- 0.6 p.p.b.; P < 0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed. CONCLUSIONS: These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.

Effects of fixed compared to automatic CPAP on sleep in Obstructive Sleep Apnoea Syndrome.

BACKGROUND: Automatic CPAP has been developed to improve CPAP efficiency and compliance. Continually matching the effective pressure may be associated to more frequent arousals that could disturb sleep. The aim of the present study was to compare sleep architecture after one month's home therapy with CPAP or with an AutoCPAP device. METHODS: Twenty OSAS patients (18 M / 2 F) after polysomnographic study with CPAP titration received either an automatic (AutoSet T, ResMed, Sydney, Australia) or a fixed level CPAP machine in a random, single blind fashion for one month. At the end of the home treatment period polysomnography was repeated while CPAP was administered by the same machine used at home. RESULTS: There was no significant difference between groups in terms of age (50.0 vs 45.5, NS), sex, BMI (38.3 vs 35.1, NS), RDI (45.4 vs 48.0, NS), and CPAP effective level (9.8 vs 10.8, NS). After one month of therapy the correction of sleep respiratory disturbances and of sleep structure was satisfactory in both groups. No difference in any polysomnographic variable or in subjective sleepiness was found at re-evaluation. CONCLUSIONS: The results of this study demonstrate that on average CPAP administered by a fixed CPAP machine and by the AutoSet T autoCPAP device has similar effects in improving respiratory function during sleep, nocturnal sleep architecture, and subjective daytime sleepiness after a one-month therapy. As autoCPAP devices are more expensive than fixed CPAP machines, their prescription should be considered only after a clear demonstration of an increase in compliance to treatment by these devices.

Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome.

OBJECTIVES: To evaluate sleep quality, sleep-related symptoms, and degree of excessive daytime sleepiness (EDS) in severe obesity, independently of obstructive sleep apnoea syndrome (OSAS). DESIGN: A cross-sectional study. SETTING: Primary-care setting. SUBJECTS, MAIN OUTCOME MEASURES: Anthropometric parameters, respiratory function data and sleep related symptoms were evaluated in 78 severely obese patients (aged 16-75 years) without OSAS and in 40 healthy sex- and age-matched normal weight subjects, who underwent a full-night polysomnography. RESULTS: Obese patients and control subjects had similar sleep latency and rapid eye movement (REM) latency, but they showed lower percentage of REM (P < 0.01) and sleep efficiency (P < 0.05) than controls. All sleep-related symptoms (observed or reported apnoea, awakenings, choking and unrefreshing sleep) were significantly more frequent in obese patients than in control subjects. Loud snoring was present in 46.7% of the obese patients and in 8.1% of the control individuals (P < 0.01). Excess daytime sleepiness was reported by 34.7% of the obese patients and by 2.7% of the normal weight subjects (P < 0.01). The Epworth Sleepiness Scale (ESS) was higher in the obese group than in the control group (P < 0.01), whereas arousals were not different between the two groups. CONCLUSIONS: This study clearly shows that severe obesity, even in the absence of OSAS, is associated with sleep-related disorders and EDS. All these alterations may be partly responsible for a lower quality of life, a higher prevalence of medical complications, an increased risk of occupational injury, and both social and family problems characterizing obese patients, independently of the presence of OSAS.

Surgical considerations in needle localization procedures.

There is an increasing need for needle localization biopsies. Cancers so detected are usually at an earlier stage and should result in an increased cure rate. The surgeon involved in these procedures should, of necessity, be proficient in evaluating mammographic abnormalities, since there is considerable variation in the way they are reported by various radiologists. Localization can be accomplished with various hooked wires or dye, but accuracy of placement is more important than the method used and this point is well understood by cooperative radiologists. Since 70-80% of these lesions will be benign, cosmesis should be kept in mind. Incisions should be placed centrally, if possible, and the volume excised should be minimal and not lead to deformity. When poorly localized, excision of these lesions can be a trying experience for the experienced surgeon.

Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: correlation with clinical outcome of anti-estrogen therapy.

We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end-point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase-type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue-type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor-mediated. (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone-receptor-positive tumors. (v) Of 20 evaluable patients with lymph-node and receptor-positive breast cancer who received adjuvant anti-estrogen therapy, 11 were identified as estradiol-sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow-up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol-insensitive, 4 developed metastases within 3+ years of follow-up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti-estrogen therapy, underscore the potential usefulness of the organ culture approach.

Breast carcinoma in situ.

A total of 150 patients with in situ breast cancer were treated from 1970 through 1976, with a median follow-up of 11.5 years. There were 42 patients with microinvasion and 25 with bilateral disease, analyzed separately. Eight patients who became unavailable for follow-up within five years (but who had no evidence of disease [NED]) were excluded. Eighty-five patients had ductal carcinoma in situ, 43 had lobular carcinoma in situ, and 22 had a mixed type. Modified radical mastectomy was done in 112 cases. One of 128 patients had positive axillary nodes; axillary dissection is not indicated for in situ breast cancer. Of the 150 patients, one with ductal disease died of disease. Six died of other causes, free of disease. Of 18 treated by excision alone, two underwent mastectomy for recurrence and had NED. Patients with microinvasion had involved nodes in 10%, and 94% had NED. However, all bilateral cases had NED.

Predictors of recurrence in stage I (T1N0M0) breast carcinoma.

A ten-year follow-up study of 382 women with Stage I (T1N0M0) breast carcinoma revealed recurrence and/or death due to cancer in 16% of the patients. Among 134 patients (35%) with a primary tumor 1.0 cm or less in diameter (Group A), 7% had recurrences and 5% died of breast carcinoma. Recurrences were observed in 21% of the 248 women with a tumor 1.1-2.0 cm in diameter (Group B), and 15% died of disease. These differences in recurrence and mortality rates were statistically significant. All recurrences were due to infiltrating duct or lobular carcinoma which accounted for 91% of the 382 carcinomas. Most strongly linked to recurrence was the finding of tumor emboli in lymphatics of the breast. This was found in 23 Group B patients and ten of them (43%) died of disease. No recurrences were observed among the seven Group A patients with lymphatic emboli. Other features associated with a significantly increased risk of recurrence were poorly differentiated carcinoma, marked lymphoid reaction to tumor, and menarche before age 12 years or after age 14 years. No combination of variables proved to identify a subset of patients with an especially increased or low risk of recurrence. Stage I patients with lymphatic tumor emboli in the breast surrounding a carcinoma 1.1-2.0 cm in diameter have a sufficient risk for recurrence to warrant consideration of adjuvant systemic therapy. A very low risk of recurrence was observed for the following: any tumor 1.0 cm or smaller; and tubular, medullary or colloid carcinoma up to 2.0 cm.

Juvenile papillomatosis (Swiss cheese disease) of the breast.

Thirty-seven cases of juvenile papillomatosis of the breast were reviewed. The average age was 19 years (range 10-44 years). On examination the patients usually had a localized, multinodular mass that was interpreted as a fibroadenoma. Microscopically, typical lesions featured papillomatosis, sometimes with severe atypia, cysts with or without apocrine metaplasia, duct stasis, and sclerosing adenosis. In one case the breast with papillomatosis adenosis. In one case the breast with papillomatosis has remained free of carcinoma, but at the time of biopsy the patient had secretory carcinoma of the other breast. Papillomatous changes were not observed in the breast with carcinoma. Another woman had lobular carcinoma in situ coexisting with juvenile papillomatosis. After an average follow-up of 8 years, no subsequent carcinoma has been found. Thus, there appears to be little risk for early onset of carcinoma, but without additional follow-up the long-term assessment of this disorder remains uncertain. We recommend that a patient with juvenile papillomatosis have a thorough clinical examination of the breasts at least once a year.