How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1.

The aim of the present study was to determine whether the combination of low forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) ratio with normal FEV(1) represents a physiological variant or a sign of early airflow obstruction. We studied 40 subjects presenting with low FEV(1)/VC, but FEV(1) within the range of normality predicted by European Respiratory Society reference equations, and 10 healthy controls. All subjects completed two questionnaires and underwent comprehensive pulmonary function testing, which included methacholine challenge and single-breath nitrogen wash-out. According to the questionnaires, the subjects were assigned to three groups, i.e. rhinitis (n = 8), bronchial asthma (n = 13) and chronic obstructive pulmonary disease (COPD; n = 12). Subjects with negative responses to questionnaires were assigned to an asymptomatic group (n = 7). Airway hyperresponsiveness was found in four subjects of the rhinitis group, all of the asthma group, and 10 of the COPD group; in the last two groups, it was associated with signs of increased airway closure and gas trapping. Bronchodilator response to salbutamol was positive in only a few individuals across groups. In the asymptomatic group, no significant functional changes were observed, possibly suggesting dysanaptic lung growth. In subjects with low FEV(1)/VC and normal FEV(1), questionnaires on respiratory symptoms together with additional pulmonary function tests may help to clarify the nature of this pattern of lung function.

Detection of influenza A(H1N1)pdm09 virus in a patient travelling from Shanghai to Italy in July 2018: an uncommon clinical presentation in a non-seasonal period.

Influenza is one of the most common infectious diseases in travellers, especially in those returning from subtropical and tropical regions. In late June 2018 an influenza A(H1N1)pdm09 virus infection was diagnosed in a 36-years-old man, returned from a travel in Shanghai and hospitalized at the Ospedale Policlinico San Martino, Genoa, Italy, with a diagnosis of fever and an uncommon clinical presentation characterised by a persistent leukopenia. Phylogenetic analysis revealed a closeness with influenza A(H1N1)pdm09 strains circulating in the US in May-June 2018. Prompt recognition of influenza infection led to a proper case management, demonstrating the crucial role of the continuous influenza surveillance programme.

Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation.

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations. No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33+/-0.55 L, forced expiratory volume in one second (FEV(1)) by 0.31+/-0.50 L, total lung capacity (TLC) by 0.39+/-0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) by 15+/-12%. At 12 months, TLC decreased by 0.43+/-0.36 L and D(L,CO )by 8+/-8%. With standard challenge, no significant changes in FEV(1) response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements. In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.

Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation.

We determined the dose-response curves to inhaled methacholine (MCh) in 16 asthmatic and 8 healthy subjects with prohibition of deep inhalations (DIs) and with 5 DIs taken after each MCh dose. Flow was measured on partial expiratory flow-volume curves at an absolute lung volume (plethysmographically determined) equal to 25% of control forced vital capacity (FVC). Airway inflammation was assessed in asthmatic subjects by analysis of induced sputum. Even when DIs were prohibited, the dose of MCh causing a 50% decrease in forced partial flow at 25% of control FVC (PD(50)MCh) was lower in asthmatic than in healthy subjects (P < 0.0001). In healthy but not in asthmatic subjects, repeated DIs significantly decreased the maximum response to MCh [from 90 +/- 4 to 62 +/- 8 (SD) % of control, P < 0.001], increased PD(50)MCh (P < 0.005), without affecting the dose causing 50% of maximal response. In asthmatic subjects, neither PD(50)MCh when DIs were prohibited nor changes in PD(50)MCh induced by DIs were significantly correlated with inflammatory cell numbers or percentages in sputum. We conclude that 1) even when DIs are prohibited, the responsiveness to MCh is greater in asthmatic than in healthy subjects; 2) repeated DIs reduce airway responsiveness in healthy but not in asthmatic subjects; and 3) neither airway hyperresponsiveness nor the inability of DIs to relax constricted airways in asthmatic subjects is related to the presence of inflammatory cells in the airways.

Mortality among silicotics in Genoa, Italy, from 1961 to 1987.

A historical cohort mortality study conducted among 515 silicotic subjects revealed higher than expected risks for all causes [standardized mortality ratio (SMR) 1.89], respiratory tract diseases (SMR 8.89), silicotuberculosis (SMR 27.00), respiratory tract cancers (SMR 3.14), and lung cancer (SMR 3.50). Mortality from cardiovascular diseases was lower than that expected (SMR 0.51). Lung cancer risk increased with duration of occupational exposure (SMR 2.80, 2.99, and 5.02 for 14, 15-29, and 30 years of employment, respectively). Lung cancer risk was higher for the silicotics without tuberculosis (SMR 3.72) than for those with tuberculosis (SMR 2.83). Indirect adjustment for smoking habits, including number of cigarettes smoked per day, showed that smoking would have been responsible for a maximum risk of 1.77. Thus smoking may have explained 50% of the observed excess mortality from lung cancer.

[Changes in lipoglycoprotein metabolism in toxic fatty liver]. / Alterazioni del metabolismo lipoglicoproteico nelle epatosteatosi tossiche.

BACKGROUND: A number of agents that produce liver injury also cause the accumulation of an abnormal amount of fat, predominantly triglycerides (TGs) in the parenchymal cells. Fatty liver (FL) is the result of an hepatocyte imbalance between the rate of synthesis and output of TGs into the plasma. TGs are not secreted as such, but combined with a glycoprotein moiety, and particularly with the very low density lipoproteins (VLDLs). This fraction is involved in the transport of hepatic TGs to extrahepatic tissues. FL can be induced by either acute or chronic administration of ethanol (EtOH), and/or several haloalkanes (carbon tetrachloride, CCl4; 1.2-dichloroethane, DCE; 1.1.2.2-tetrachloroethane, TTCE), both in laboratory animals and in man. Since the pathogenesis of this disease is a crucial problem, as yet undefined, the purpose of this article is to summarize the studies which have unraveled some of the mechanisms involved in FL, particularly the role played by impaired lipoglycoproteins (LGP) metabolism in rat liver. DISCUSSION: An important element in the pathogenesis of EtOH- and haloalkanes-induced FL is the impairment of hepatic secretion of VLDLs, which occurs soon after poisoning. Various steps of the secretory pathway are probably involved in the expression of such damage. The intoxication of rats with these xenobiotics leads to an early impairment of the hepatocyte system responsible for terminal glycosylation and maturation of LGP at the level of three different subfractions (F1, F2 and F3) of purified Golgi apparatus (GA). The earliest functional change is a block of LGP transit through the GA cisternae and vesicles, both in isolated hepatocyte model and in the whole animal. The glycosylation of LGP is a multistep process which starts in the rough endoplasmic reticulum (RER), and comes to its end in the GA. Dolichols (Dol) are a family of long-chain polyisoprenoid alcohols, present either as neutral free-Dol and dolichyl-phosphate (Dol-P). The latter acts as a glycosyl carrier across the RER membranes in the initial steps of LGP biosynthesis. Nearly all the other reactions occur in GA, where free-Dol have a role either in terminal LGP processing or in their secretion into the blood stream. Several investigations indicated that both EtOH and haloalkanes (CCl4, DCE, and TTCE) may selectively and precociously impair the total microsomes (TM) and GA pool of Dol, particularly in F1. Lipid peroxidation appears to be the fundamental mechanism involved. CONCLUSIONS: Such results, obtained in several works, point out a key role played in FL by selective impairment of MT and GA processes which provide for the synthesis, maturation and release of hepatic LGP.

[Toxicity of 4-chloro-2-nitroaniline and 2-chloro-4-nitroaniline to isolated rat hepatocytes]. / Tossicità della 4-cloro-2-nitroanilina e della 2-cloro-4-nitroanilina su epatociti isolati di ratto.

The toxicity of 4-chloro-2-nitroaniline (4C2NA) and 2-chloro-4-nitroaniline (2C4NA) was investigated on isolated rat hepatocytes following 1-3 hours of exposure to 0.2 and/or 2 mM of these xenobiotics. The higher of the two concentrations appeared to induce a statistically significant loss of cellular viability (p less than 0.01 compared to control), judged by Trypan Blue staining, after 3 hours of incubation with these substances means = 58, SD = 7%; and means = SD = 7%; for 4C2NA and 2C4NA, respectively). Furthermore, both chloronitroanilines produced an hepatocellular and microsomal damage demonstrated by conspicuous changes in LDH and G-6-Pase activities (p less than 0.01). The exposure to 2 mM of both 4C2NA and/or 2C4NA produced a marked depletion of the intracellular pool of GSH after 3 hours (13 mM/10(6) and 10 mM/10(6) cells, respectively; p less than 0.01). Thus it seems possible that 2C4NA may induce a more severe cellular damage than that induced by 4C2NA.

Feasibility of protein-sparing modified fast by tube (ProMoFasT) in obesity treatment: a phase II pilot trial on clinical safety and efficacy (appetite control, body composition, muscular strength, metabolic pattern, pulmonary function test).

Anecdotal data in the last few years suggest that protein-sparing modified diet (PSMF) delivered by naso-gastric tube enteral (with continuous feeding) could attain an significant weight loss and control of appetite oral feeding, but no phase II studies on safety and efficacy have been done up to now. To verify the safety and efficacy of a protein-sparing modified fast administered by naso-gastric tube (ProMoFasT) for 10 days followed by 20 days of a low-calorie diet, in patients with morbid obesity (appetite control, fat free mass maintenance, pulmonary function tests and metabolic pattern, side effects), 26 patients with a BMI ≥30 kg/m2 have been selected. The patients had to follow a protein-sparing fast by enteral nutrition (ProMoFasT) for 24 h/day, for 10 days followed by 20 days of low-calorie diet (LCD). The endpoint was represented by body weight, BMI, abdominal circumference, Haber's appetite test, body composition by body impedance assessment (BIA), handgrip strength test, metabolic pattern, pulmonary function test. Safety was assessed by evaluation of complications and side effects of PSMF and/or enteral nutrition. In this report the results on safety and efficacy are described after 10 and 30 days of treatment. After the recruiting phase, a total of 22 patients out of 26 enrolled [14 (63.6 %) females] were evaluated in this study. Globally almost all clinical parameters changed significantly during first 10 days. Total body weight significantly decreased after 10 days (∆-6.1 ± 2; p < 0.001) and this decrease is maintained in the following 20 days of LCD (∆ = -5.88 ± 1.79; p < 0.001). Also the abdominal circumference significantly decreased after 10 days [median (range): -4.5 (-30 to 0); p < 0.001] maintained then in the following 20 days of LCD [median (range) = -7 (-23.5 to -2); p < 0.001]. All BIA parameters significantly changed after 10 and 30 days from baseline. All parameters except BF had a significant change after 10 days of treatment while the difference at 30 days was lower than at 10 days for TBW, FFM and MM with no significant differences from baseline for the last two characteristics. For VAS appetite the difference was significant after 10 days and the decrease in appetite was maintained at 30 days with no significant difference (p = 0.83) between 10 and 30 days. No significant differences in the first 30 days were detected for PA and for both left and right hand grip strength. Particularly, a significant reduction of 1.82 kg in FFM after 10 days was detected, but not after 30 days. In contrast, a decrease of 3.8 kg of BF is observed after 30 days. As far as the respiratory functional tests (RFT) are concerned, a significant difference at 10 days was globally observed for functional residual capacity (p = 0.012) and expiratory reserve volume (p = 0.025). There are no reported major complications and side effects resulting from the enteral nutrition or PSMF. In particular, cardiac arrhythmias have not been reported. From the clinical point of view the PSMF with naso-gastric tube (ProMoFasT) method appears safe, it is associated with a significant weight loss related to decrease of FM and not to loss of FFM and appetite decreases. It is relevant that the RFT are significantly improved after only 10 days suggesting the efficacy of this regime in short period, too. These preliminary data underline the necessity to increase the number of RCT for this method, which could represent a possible alternative to other methodologies, such as the intragastric balloon, in particular when it is recommended to improve RFT before bariatric, gynecological, orthopedic and lymphatic surgery.

Upper abdominal surgery: does a lung function test exist to predict early severe postoperative respiratory complications?

We evaluated the capacity to predict severe respiratory complications (SRCs) following upper abdominal surgery (UAS) by using the results of a respiratory questionnaire and preoperative pulmonary function tests. Lung volumes, flows and transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361 consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h after UAS by clinical examination and chest radiography. Univariate and stepwise multiple logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each single input variable, and to determine which indices best predicted outcome. These patients had a 1% mortality rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best predictors for SRCs by multiple analysis were: preoperative current hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV) (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The algorithm thus obtained (logit theta) was extremely sensitive (84%), specific (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to a lesser extent percentage predicted values both of forced expiratory volume in one second and transfer factor of the lung for carbon monoxide, have a significant predictive capacity for severe respiratory complications following upper abdominal surgery.

Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane.

BACKGROUND: 1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum. METHODS: Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. RESULTS: After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars). CONCLUSIONS: Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.