Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Improving the cadmium-induced centriacinar emphysema model in rats by concomitant anti-oxidant treatment.

1. The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N-acetylcysteine (NAC) administration. 2. Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2- and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3. Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4. Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2-treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 +/- 2 vs 127 +/- 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2-treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2-treated rats. 5. In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2-induced fibrotic component of centriacinar emphysema.

Hipoplasia pulmonar en el adulto / Lung hypoplasia in the adult

No disponible

Avances en el manejo del asma bronquial / Advances in the management of bronchial asthma

No disponible

Increased collagen deposition correlated with lung destruction in human emphysema.

BACKGROUND: To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. METHODS: Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. RESULTS: The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. CONCLUSIONS: Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

Effect of pulmonary perfusion on the slopes of single-breath test of CO2.

The objective of this study was to evaluate the effects of lung perfusion on the slopes of phases II (S(II)) and III (S(III)) of a single-breath test of CO(2) (SBT-CO(2)). Fourteen patients submitted to cardiac surgery were studied during weaning from cardiopulmonary bypass (CPB). Pump flow was decreased in 20% steps, from 100% (total CPB = 2.5 l.min(-1).m(-2)) to 0%. This maneuver resulted in a progressive and opposite increase in pulmonary blood flow (PBF) while maintaining ventilator settings constant. SBT-CO(2), respiratory, and hemodynamic variables remained unchanged before and after CPB, reflecting a constant condition at those stages. S(III) was similar before and after CPB (19.6 +/- 2.8 and 18.7 +/- 2.1 mmHg/l, respectively). S(III) was lowest during 20% PBF (8.6 +/- 1.9 mmHg/l) and increased in proportion to PBF until exit from CPB (15.6 +/- 2.2 mmHg/l; P < 0.05). Similarly, S(II) and the CO(2) area under the curve increased from 163 +/- 41 mmHg/l and 4.7 +/- 0.6 ml, respectively, at 20% PBF to 313 +/- 32 mmHg/l and 7.9 +/- 0.6 ml (P < 0.05) at CPB end. When S(II) and S(III) were normalized by the mean percent expired CO(2), they remained unchanged during the protocol. In summary, the changes in PBF affect the slopes of the SBT-CO(2). Normalizing S(II) and S(III) eliminated the effect of changes in the magnitude of PBF on the shape of the SBT-CO(2) curve.

Lower pulmonary diffusing capacity in the prone vs. supine posture.

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Qc). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, Dl(CO) was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: Dl(CO,corr) supine vs. prone: 32.6 +/- 2.3 (SE) vs. 30.0 +/- 2 ml x min(-1) x mmHg(-1) stpd; RB: Dl(CO,corr) supine vs. prone: 30.2 +/- 2.2 (SE) vs. 27.8 +/- 2.0 ml x min(-1) x mmHg(-1) stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Qc between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.

[Reliability of Venturi oxygen therapy systems]. / Fiabilidad de los sistemas de Venturi en la oxigenoterapia.

Venturi systems are among the most widely used devices for delivering oxygen therapy. Nevertheless, rigorous quality control of their reliability is lacking. In this study we used mass spectrometry to evaluate Venturi systems sold by various companies in Spain. We also studied tolerance under various conditions (changes in oxygen flow and with increased system resistance). Fixed systems were found to comply well with recommendations, whereas none of the variable systems complied. One system (Oxigem Variable) was unable to provide an oxygen concentration below 31% when set to deliver at 24% to 28%. We conclude that the variable masks available in Spain do not comply with European Union recommendations and the range of error of one of them (Oxigem Variable) means it is not clinically useful. Fixed systems were the most reliable ones in our market, and airlife and intersurgical devices were the variable systems that best approximated the reliability of fixed systems.

Fiabilidad de los sistemas de Venturien la oxigenoterapia / Reliability of Venturi oxygen therapy systems

Los sistemas de Venturi son unos de los productos más utilizados para la administración de la oxigenoterapia. A pesar de su extendido empleo en la práctica clínica habitual, se carece de rigurosos controles de calidad sobre su fiabilidad. En este trabajo se analizan por espectrometría de masas, según la normativa de la Unión Europea (UE), los sistemas de Venturi de distintas casas proveedoras disponibles en el mercado español. Se evalúa también la tolerancia de los sistemas ante diversas circustancias (cambios de flujo de oxígeno y aumento de resistencias en el sistema). Se ha encontrado que los sistemas fijos se adaptan bien a la normativa, mientras que ninguno de los sistemas variables cumple los requisitos que establece esta normativa, y un sistema (Oxigem variable) es incapaz de dar, para concentraciones del 24-28 por ciento, una concentración de O2por debajo del 31 por ciento. En conclusión, en nuestro mercado las mascarillas variables no cumplen la normativa UE y una de ellas (Oxigem variable) tiene un rango de error que no permite su uso en la práctica clínica. Los más fiables en nuestro estudio fueron los sistemas fijos y, dentro de los variables, los de Airlife e Intersurgical se aproximaban a éstos (AU)

[Non-invasive ventilation in patients with severe hypercapnic encephalopathy in a conventional hospital ward]. / Ventilación no invasiva en pacientes con encefalopatía hipercápnica grave en una sala de hospitalización convencional.

OBJECTIVE: To report our experience with non-invasive ventilation (NIV) at two levels of pressure (Bi-PAP) on a general respiratory medicine ward with patients in hypercapnic impaired consciousness and/or coma who had not previously been in an intensive care unit (ICU). METHODS: This was a prospective study of 13 patients, mean age 81 years (65-96), treated with NIV through a face mask. Ten had chronic obstructive pulmonary disease, with a mean FEV1 in stable condition of 35.2 14.6%. Glasgow scores upon admission were >/= 7. Arterial gases were monitored until suspension of NIV. RESULTS: After NIV for a mean 19 5 h/day in the first 48 hours and later of 6 1 h/day until a total of 74 9 h, 9 patients (69%) survived. The mean initial pH for these patients was 7.17 0.028 and the mean initial pCO2 was 101 9 mm Hg. In 7 cases (78%), coma was reversed in the first 48 h and a significant improvement in pH was observed in the 12-24 h analysis. Mean pH upon discharge was 7.44 0.013 and mean pCO2 was 54 2.8 mmHg. Four patients died, even though their initial or subsequent arterial gases at 12-24 h were not significantly different from those of the survivors. CONCLUSION: NIV on a general respiratory medicine ward can offer an alternative to oro-tracheal intubation for patients with hypercapnic impaired consciousness and/or coma who do not meet the criteria for admission to the ICU.

Ventilación no invasiva en pacientes con encefalopatía hipercápnica grave en una sala de hospitalización convencional / Non-invasive ventilation in patients with severe hypercapnic encephalopathy in a conventional hospital ward

OBJETIVO: Mostrar nuestra experiencia con la ventilación no invasiva (VNI) con doble nivel de presión (BIPAP) en una sala general de neumología en pacientes en estupor o coma hipercápnicos sin criterios de ingreso en unidad de cuidados intensivos (UCI).MATERIAL Y MÉTODOS: Estudio prospectivo de 13 pacientes, edad media 81 años (límites, 65-96), 10 pacientes presentaban exacerbación de enfermedad pulmonar obstructiva crónica (EPOC) con volumen espiratorio forzado en el primer segundo (FEV1) medio en situación estable de 35,2 ñ 14,6 per cent, índice de Glasgow ingreso 7, tratados con VNI mediante mascarilla facial. Se realizaron controles gasométricos hasta la suspensión de la VNI.RESULTADOS: Tras una media de ventilación de 19 ñ 5 h/día en las primeras 48 h y posteriormente 6 ñ 1 h/día hasta un promedio total de 74 ñ 9 h, sobrevivieron 9 pacientes (69 per cent).En este grupo los valores iniciales medios de pH y pCO2 fueron de 7,17 ñ 0,028 y 101 ñ 9 mmHg, respectivamente; de ellos en 7 casos (78 per cent) se revirtió el coma en las primeras 48 h y se observó una mejoría significativa en el valor de pH en el control de las 12-24 h. Los valores medios al alta de pH y pCO2 fueron 7,44 ñ 0,013 y 54 ñ 2,8 mmHg, respectivamente.Fallecieron 4 pacientes, cuyos valores gasométricos iniciales o evolutivos hasta las primeras 12-24 h no presentaron diferencia significativa con el grupo de supervivientes.CONCLUSIÓN: La aplicación de la VNI en una sala general de neumología puede constituir una alternativa a la intubación orotraqueal (IOT) en pacientes en situación de estupor o coma hipercápnicos que no cumplen criterios de ingreso en UCI (AU)

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.

Single-breath washouts in a rotating stretcher.

Vital capacity single-breath washouts using 90% O2-5% He-5% SF6 as a test gas mixture were performed with subjects sitting on a stool (upright) or recumbent on a stretcher (prone, supine, lateral left, lateral right, with or without rotation at end of inhalation). On the basis of the combinations of supine and prone maneuvers, gravity-dependent contributions to N2 phase III slope and N2 phase IV height in the supine posture were estimated at 18% and 68%, respectively. Whereas both He and SF6 slope decreased from supine to prone, the SF6-He slope difference actually increased (P = 0.015). N2 phase III slopes, phase IV heights, and cardiogenic oscillations were smallest in the prone posture, and we observed similarities between the modifications of He and SF6 slopes from upright to prone and from upright to short-term microgravity. These results suggest that phase III slope is partially due to emptying patterns of small units with different ventilation-to-volume ratios, corresponding to acini or groups of acini. Of all body postures under study, the prone position most reduces the inhomogeneities of ventilation during a vital capacity maneuver at both inter- and intraregional levels.

Melanoptysis as a complication of fibreoptic bronchoscopy.

The case is presented of a coal miner with bilateral masses of progressive massive fibrosis, who developed acute cavitation following fibreoptic bronchoscopy and biopsies. Indeed, immediately upon bronchoscopy with transbronchial biopsy, there was expectoration of abundant melanoptysis. Three days later, the chest radiograph showed a cavity and the patient again coughed up black material, in the context of pulmonary infection. One week later, there was complete emptying of the conglomerate mass. To the authors' knowledge, this is the first reported case of a conglomerate mass of progressive massive fibrosis which cavitated as a result of bronchoscopy.