TITLE: 
A new prototype of an electronic jet-ventilator and its humidification
		  system



ABSTRACT.BACKGROUND:
Adequate humidification in long-term jet ventilation is a critical
				aspect in terms of clinical safety.

ABSTRACT.AIM:
To assess a prototype of an electronic jet-ventilator and its
				humidification system.

ABSTRACT.METHODS:
Forty patients with respiratory insufficiency were randomly
				allocated to one of four groups. The criterion for inclusion in this study was
				respiratory insufficiency exhibiting a Murray score above 2. The four groups of
				patients were ventilated with three different respirators and four different
				humidification systems. Patients in groups A and B received superimposed
				high-frequency jet ventilation (SHFJV) by an electronic jet-ventilator either
				with (group A) or without (group B) an additional humidification system.
				Patients in group C received high-frequency percussive ventilation (HFPV) by a
				pneumatic high-frequency respirator, using a hot water humidifier for warming
				and moistening the inspiration gas. Patients in group D received conventional
				mechanical ventilation using a standard intensive care unit respirator with a
				standard humidification system. SHFJV and HFPV were used for a period of 100 h
				(4days).

ABSTRACT.RESULTS:
A significantly low inspiration gas temperature was noted in
				patients in group B, initially (27.2 ± 2.5°C) and after 2 days
				(28.0 ± 1.6°C) (P < 0.05). The percentage of relative
				humidity of the inspiration gas in patients in group B was also initially
				significantly low (69.8 ± 4.1%; P < 0.05) but rose to an average
				of 98 ± 2.8% after 2 h. The average percentage across all four groups
				amounted to 98 ± 0.4% after 2 h. Inflammation of the tracheal mucosa was
				found in patients in group B and the mucosal injury score (MIS) was
				significantly higher than in all the other groups. Patients in groups A, C and
				D showed no severe evidence of airway damage, exhibiting adequate values of
				relative humidity and temperature of the inspired gas.

ABSTRACT.CONCLUSION:
The problems of humidification associated with jet ventilation can
				be fully prevented by using this new jet-ventilator. These data were sustained
				by nondeteriorating MIS values at the end of the 4-day study period in groups
				A, C and D.

BODY.INTRODUCTION:
High-frequency jet ventilation (HFJV) has proved to be an alternative
		  to conventional mechanical ventilation (CMV) [1,2,3,4]. The major advantage of HFJV lies in the improvement of the
		  mucociliary transport system [5], the recruitment of
		  atelectatic areas [6], and the improvement of oxygenation
		  [7,8], maintaining very low tidal
		  volumes to avoid lung barotrauma [9]. However, one of the
		  critical issues concerning HFJV is the adequate humidification and warming of
		  the inspired gases [10]. Specific problems derive from
		  the physical phenomena of the high velocity of the jet-stream, the
		  Joule-Thompsen effect and the Venturi effect [11],
		  causing low temperature and low relative humidity of the inspired gases [12,13].
There are several forms of HFJV [14]. Combined
		  high-frequency jet ventilation (CHFJV) is a technique that requires a
		  conventional respirator (endotracheal tube) and a high-frequency jet-ventilator
		  (endotracheal jet tube) [15]. A special type of the
		  CHFJV is the superimposed high-frequency jet ventilation (SHFJV), which is a
		  time-regulated, pressure-controlled ventilation technique. It is characterized
		  by the simultaneous application of a low-frequency jet stream and a
		  high-frequency jet stream, resulting in the superposition of two jet streams
		  with different frequencies [16]. This ventilation
		  technique is managed by one respirator. Volumetric diffusive respiration is a
		  type of ventilation (using, for example, the VDR 4, Percussionaire Corp, Idaho,
		  USA) named high-frequency percussive ventilation (HFPV) [17]. Although these techniques have been described in the
		  literature, they have not been rigorously compared to each other in long-term
		  applications. There are several humidification systems for CMV [18] and HFJV [19,20], for example, hot water humidifiers, cold water
		  humidifiers and heat and moisture exchangers. The most commonly used
		  humidification system in our institution is the hot water humidifier (Aquapor,
		  Type 8406640, Draeger Corp, Luebeck, Germany).
The aim of this study was to show that the problems of humidification
		  associated with SHFJV can be prevented by using the correct humidification
		  system. Proper methods for showing possible epithelial damage were used.

BODY.MATERIAL AND METHODS:
After approval by the institutional Ethics Committee and informed
		  consent, 40 intensive care unit (ICU) patients (Table 1)
		  were randomly allocated to one of four groups (A, B, C or D; 10 patients in
		  each group). The inclusion criterion was respiratory insufficiency due to
		  pneumonia or involvement of the lungs in multi-organ dysfunction syndrome. All
		  patients showed a Murray score [21] (Table
		  2) above 2.0, fulfilling the criteria for acute
		  respiratory distress syndrome (ARDS) or acute lung insufficiency (ALI)
		  according to the European American Consensus Conference 1994 (Table
		  2). The mean number of CMV respiration days before group
		  allocation was 2.2 days. The median age of the 16 female and 24 male patients
		  was 67 years, ranging from 55 to 79 years.
All patients were sedated with midazolam 0.1–0.15 mg/kg per h and
		  sufentanil 0.01–0.015 mg/kg per h, and optionally with ketamine 1–2 mg/kg per h.
		  Fluid and catecholamines were administered to achieve a pulmonary capillary
		  wedge pressure (PCWP) between 12 and 18 mmHg, a cardiac index (CI) above
		  2.5 l/min per m2, and a systemic vascular resistance index (SVRI)
		  between 600 and 1500 dyn × s/cm5 per m2. Antibiotic
		  therapy was adapted according to the results of bacterial cultures of the
		  tracheobronchial secretion. Red packed cells where given to restore blood
		  volume when required and to maintain the hematocrit >32%. Hemodynamic
		  variables were assessed through central venous and peripheral arterial lines.
		  In eight patients, a Swan-Ganz pulmonary artery catheter was inserted.
Patients in group A received SHFJV by a prototype of an electronic
		  jet-ventilator (Alexander 1, Festo Corp, Vienna, Austria) (Fig. 1). The Alexander 1 works in an open system, providing a
		  low-frequency jet stream ranging from 4 to 40 breaths/min that influences the
		  peak pressure, and a high-frequency jet stream ranging from 60 to 990
		  breaths/min that influences the positive end-expiratory pressure (PEEP). Both
		  jet streams are simultaneously applied to the patient using a newly developed
		  jet adapter [22]. This plastic jet adapter (T-connector
		  with a luer lock, Willy RãSCH AG, Kermen, Germany) consists of a T-piece
		  and four central small-bore cannulas that can be connected to any commercially
		  available endotracheal tube, avoiding reintubation with an endotracheal jet
		  tube when beginning SHFJV. The high-frequency and low-frequency ventilation is
		  performed with two jet nozzles which have been designed according to optimal
		  dynamic flow measurements. Two further jet nozzles are used for continuous
		  airway pressure monitoring and for passing saline solution into the jet stream.
		  Next to the T-piece there is a lockable aperture that can be used for
		  suctioning or bronchoscopy, without loss of PEEP.
For humidification, we used a combined humidification and warming
		  system for patients in group A. The entrained gases (bias flow) were humidified
		  by a hot water humidifier (Aquapor) and the inspiration gas bubbles through a
		  waterbath heated by an immersed heating element. Gas leaving the device is
		  saturated with water vapor and is heated to a pre-set temperature. The absolute
		  humidity can be altered by changing the temperature of the waterbath.
Humidification of the jet gas was achieved by a continuous infusion of
		  0.9% saline via a separate cannulla in the jet adapter. This was propelled and
		  nebulized by the high-pressure jet stream, starting at 20 ml/h. The saline
		  solution was warmed to 39°C by a fluid warmer (HL-90 INT, Level 1
		  Technologies Corp, Rockland, Massachusetts, USA) before it reached the jet
		  adapter (ie, an additional humidification system). This allows for a possible
		  warm-up of 42°C to compensate for the temperature drop of the gas after
		  decompression (the Joule-Thompsen effect).
Patients in group B also used the Alexander 1, with a hot water
		  humidifier for the bias flow (Aquapor) and a continuous saline infusion for the
		  jet flow (the additional fluid warmer mentioned above was not used in patients
		  in group B).
Patients in group C received HFPV using the VDR 4, which is a
		  pneumatic time-regulated, pressure-controlled respirator that works in a closed
		  system to provide two oscillating pressure plateaus. The HFPV is generated by a
		  phasitron, causing gases in the airways to oscillate back and forth between the
		  respirator and the patient, with the fresh gas entrained from the bias flow.
		  Because of the continuous flow applied during HFPV the patient is able to
		  breathe spontaneously at any time during the respiratory cycle, and respiratory
		  weaning can be performed. This method allows conventional heater humidifiers to
		  be used. In our study we used a hot water humidifier (Aquapor).
Patients in group D received CMV using a conventional intensive care
		  respirator (Evita, Draeger Corp) in a pressure-controlled mode using a hot
		  water humidifier (Aquapor).
In all four groups, PEEP, the fractional inspiratory oxygen
		  concentration (FiO2) and inspiration to expiration time ratio (I:E)
		  were adjusted to keep arterial oxygen saturation 
		(SaO2) above 90% with the lowest possible peak airway
		  pressure and FiO2.
On the first day of the study, relative humidity measurements were
		  performed at jet ventilation commencement, and after 20 min and 2 h.
		  Consequently, data were taken only twice a day until the end of the 4-day
		  study. Values were accurate to ± 2% of relative humidity. Relative
		  humidity was measured inside the tube, at its distal end, with an electronic
		  device (E20-FXD, E u. E Elektronik Corp, Unterwiesen, Austria). This very small
		  sensor consists of a condensator with a capacity of 600 picoFarad at a relative
		  humidity of 70%. The polymer sensor changes its capacity according to the
		  amount of moisture inside the area that is measured. This chemical reaction is
		  translated into an electronic signal, which is shown on a liquid crystal
		  display (ie, monitor) outside the tube as a percentage of the relative humidity
		  inside the inspired gas flow.
The temperature was measured at the same location following the same
		  timetable as above with a temperature sensor line (21076 A, Hewlett Packard,
		  Palo Alto, California, USA). Values were accurate to ± 0.1°C.
The tracheobronchial mucosa was inspected twice a day by bronchoscopy
		  (Olympus BF Type P20D, Olympus Corp Ltd, Shirakwa, Japan) over the entire 100-h
		  study period according to a mucosal injury score (MIS). The MIS takes into
		  account the area and the extent of macroscopic epithelial damage in the
		  tracheobronchial system: area A represents the mucosa around the cuff (for
		  inspection, the tube has to be withdrawn a little); area B represents the
		  mucosa from below the cuff down to the carina; area C represents the mucosa of
		  the right mainstem bronchus; and area D represents the mucosa of the left
		  mainstem bronchus. Each area is given a number, representing the amount of
		  mucosal damage (0, no exsiccosis, no inflammation and no necrosis; 1,
		  exsiccosis as shown by a pale mucosa with no signs of epithelial damage; 2,
		  inflammation of the mucosa shown by mucosal redness and tumor; 3, necrosis
		  shown by a pale mucosa with signs of epithelial damage). Thus, the possible
		  value of the MIS ranges from 0 to 12 with damage classified as: 1–3, simple
		  damage; 4–8, significant damage; 9–12, severe damage.
The humidification rate (initially 20 ml/h) was set depending on the
		  bronchoscopic aspect of the tracheobronchial mucosa; classification above
		  'simple damage' (ie, MIS above 3) led to an increase in the
		  humidification rate up to and above 45 ml/h.
BODY.STATISTICAL ANALYSIS:
For demographic data (Table 1) and measured
			 values of relative humidity and gas temperature a Duncan test was calculted to
			 determine statistical significance. All values are expressed as mean ±
			 standard deviation. P < 0.05 was regarded as statistically
			 significant.
Since homogeneity of variances were seen, statistical evaluation was
			 performed using single factorial analysis. However, as the small number of spot
			 samples impaired the standard distribution, a nonparametric method (variance
			 analysis by Kruskal–Wallis) was also used. Both methods showed the same
			 significant differences between the groups. Furthermore, a pathanalysis was
			 calculated to check the statistical relevance of the hypothetical influence of
			 the forms of ventilation on temperature and humidity.
Figure 1A prototype of an electronic jet ventilator (Alexander 1; Festo
				Corp, Vienna, Austria). This ventilator delivers a high-frequency and a
				low-frequency jet stream simultaneously to the patient: superimposed
				high-frequency jet ventilation (SHFJV). PEEP, positive end-expiratory pressure;
				FiO2, fractional inspiratory oxygen concentration; LF, lowfrequency;
				HF, high frequency.
Table 1Patient characteristics and demographic data at study entry
Characteristic

 Age (years)
       67 ± 12
 Sex (male/female)
      24/16
 
Etiology of acute respiratory failure (n)

 Postoperative
       20
 Pneumonia
       12
 Sepsis
       8
 
Drug treatment

 Midazolam (n, mg/kg per h)
  40, 0.12 ± 0.03
 Sufentanil (n, mg/kg per h)
  40, 0.012 ± 0.003
 Ketamine (n, mg/kg per h)
  15, 1.5 ± 0.5
 
Respirator therapy (CPPV, pressure controlled mode, by
					 Evita*)

 Pmax (n, mbar)
40, 26 ± 4
 PEEP (n, mbar)
40, 10 ± 2
 FiO2 (n, %)
  40, 70 ± 16
 I:E (n, time ratio)
      40, 1:1
*Draeger Corp, Luebeck, Germany. CPPV, continuous
				positive pressure ventilation; Pmax, maximal airway pressure; PEEP, positive
				end-expiratory pressure; FiO2, fractional inspiratory oxygen
				concentration; I:E, inspiration to expiration time ratio.
Table 2Respiratory insufficiency as the inclusion criterion (Murray score
			 [21] and European American Consensus Conference 1994
			 values)
Murray Score (mean values of 40 patients)



Measured value
Points
 PaO2/FiO2
160 ± 15
3
 PEEP (mbar)
10 ± 2
2
 Compliance (ml/cmH2O)
36 ± 3
3
 X-ray quadrants
  2 ± 1
2
 Sum total

10
 Score (Sum total/4)

2.5
 
European American Consensus Conference 1994


ARDS:


 acute onset


 PaO2/FiO < 200 mmHg (peep independent)


 Bilateral infiltration on ap chest X-ray


 PCWP < 18 mmHg or absence of left atrial
					 hypertension


ALI:


 acute onset


 PaO2/FiO2 < 300 mmHg (peep
					 independent)


 Bilateral infiltration on ap chest x-ray


 PCWP < 18 mmHg or absence of left atrial
					 hypertension


PaO2, partial pressure of oxygen; FiO2,
				fractional inspiratory oxygen Concentration; PEEP, positive end-expiratory
				pressure; ARDS, acute respiratory distress syndrome; ALI, acute lung
				insufficiancy; ap, anterior-posterior; PCWP, pulmonary capillary wedge
				pressure.


BODY.RESULTS:
Prior to random allocation to the four groups, all patients were
		  conventionally ventilated (CMV using Evita) for 48–72 h. The average number of
		  ventilation days in each group was 10 days (the duration of mechanical
		  ventilation before weaning started). The overall period of ventilation was
		  18 ± 4 days.
BODY.RELATIVE HUMIDITY:
Initially, the lowest percentage of mean relative humidity (Fig.
			 2) was seen in patients in group B (69.8 ± 4.1%;
			 P < 0.05). Patients in group A showed a mean relative humidity of
			 71.2%, patients in group C showed a mean relative humidity of 92.2% and
			 patients in group D showed a mean relative humidity of 92.0%.
After 20 min of ventilation the mean relative humidity of the
			 inspiration gas was still lower in patients in group B (92.8%) compared with
			 patients in group A (96.8%), group C (97.4%), and group D (98.6%).
After 2 h of ventilation patients in all four groups showed almost
			 equivalent mean values (98 ± 0.4%). All measurements taken from this point
			 until the end of the 100-h study protocol showed no more significant changes
			 compared to the values measured after 2 h.

BODY.TEMPERATURE:
Initially, the lowest temperature measured inside the tube (Fig.
			 3) was seen in patients in group B (27.2 ± 
			 2.5°C; P < 0.05). Patients in group A had a mean gas
			 temperature of 31.4 ± 2.8°C, those in group C had a mean gas
			 temperature of 32.1 ± 2.6°C, and those in group D had a mean gas
			 temperature of 34.2 ± 2.7°C.
After 20 min of ventilation the inspiration gas temperature was still
			 lower in patients in group B (27.1 ± 1.8°C) compared with patients in
			 group A (32 ± 1.8°C), patients in group C (32.5 ± 2.3°C), and
			 patients in group D (34.1 ± 2.5°C).
After 2 h of ventilation the trend was similar (patients in group B,
			 27.1 ± 1.8°C; patients in group A, 32.4 ± 1.1°C; patients in
			 group C, 32.6 ± 1.6°C; and patients in group D, 34.3 ±
			 2.3°C).
After 2 days the values were: patients in group B, 28.0 ±
			 1.6°C; patients in group A, 33.2 ± 1.7°C; patients in group C,
			 33.2 ± 2.5°C; patients in group D, 34.5 ± 1.8°C.
After 4 days the values were: patients in group B, 28.0 ±
			 1.9°C; patients in group A, 33.0 ± 1.7°C; patients in group C,
			 33.6 ± 2.5°C; patients in group D, 34.3± 1.8°C.

BODY.MUCOSAL INJURY SCORE:
During the course of SHFJV, patients in group B showed signs of
			 epithelial lesions and inflammation of the mucosa in area B within hours
			 (MIS = 2), deteriorating on the third and fourth day (MIS = 3) (Fig. 4). During bronchoscopy, a tracheobronchial secretion was
			 removed. The bronchial epithelium (area C) showed no pathologic evidence.
			 Typical changes to the mucosa were not detected in patients in any group other
			 than those in group B.
In group A, C and D no epithelial damage could be found in any area.
			 Eight patients (group independent) who were in an intermittent prone position
			 (usually turned every 12 h) showed little tracheal damage at the end of the
			 tube.
Although one patient in group C died as a result of severe sepsis,
			 their tracheobronchial mucosa showed no adverse tissue change when compared to
			 the control group. As the period of ventilation (72 h) was probably sufficient
			 to induce any injury as a result of the humidification system, data from this
			 patient were not excluded in our comparison. The statistical relevance of the
			 hypothetical influence of the forms of ventilation on temperature and humidity
			 were checked by pathanalysis. Only group B appeared to show any influence.

BODY.HUMIDIFICATION RATE OF THE ADDITIONAL HUMIDIFICATION SYSTEM:
Initially, the humidification rate of the additional humidification
			 system was set at 20 ml/h saline solution via the jet adapter (Table
			 3). This was changed depending on the bronchoscopic
			 aspect of the tracheobronchial mucosa and the presence of dry secretion.
			 Patients in group A showed an average setting of 30 ± 10 ml/h, starting at
			 20 ml/h and rising to 40ml/h on the second day. Patients in group B showed the
			 highest demand for saline solution, with an average setting of 45 ± 5 ml/h
			 and a peak of 50 ml/h on the fourth day. Patients in groups C and D were served
			 by a hot water humidifier without an additional humidification system.
Figure 2Percentage of relative humidity (RH) of the inspiration gas for
				each group initially, after 20 min, 2 h, after 2 days and after 4 days of
				ventilation (mean± standard deviation).
Figure 3Temperature of the inspiration gas of each group initially, after
				20 min, 2 h, after 2 days and after 4 days of ventilation (mean ± standard
				deviation).
Figure 4Mucosal injury score of each group initially, after 20 min, 2 h,
				after 2 days and after 4 days of ventilation (mean± standard
				deviation).
Table 3Mucosal injury score and humidification rate settings during the
			 course of superimposed high-frequency jet ventilation

Group A
Group B
Initially


 Mucosal injury score
0
0
 Humidification rate setting (ml/h)
20
20
 
After 20 min


 Mucosal injury score
0
1
 Humidification rate setting (ml/h)
20
30
 
After 2 h


 Mucosal injury score
1
2
 Humidification rate setting (ml/h)
30
40
 
After 2 days


 Mucosal injury score
2
3
 Humidification rate setting (ml/h)
40
45
 
After 4 days


 ;Mucosal injury score
1
3
 Humidification rate setting (ml/h)
35
50


BODY.DISCUSSION:
This study yielded two major findings. Firstly, adequate
		  humidification without sufficient warming of the inspiration gas does not
		  prevent epithelial damage or inflammation. Secondly, the amount of
		  humidification needed has to be changed almost every day, sometimes even within
		  hours. Thus, regular bronchoscopy is necessary. Leaving the inspiration gas
		  temperature significantly below 30°C ('cold ventilation'),
		  even under high humidity (relative humidity above 90%), leads to epithelial
		  damage, inflammation or even necrotizing tracheobronchitis [23].

To humidify a dry gas and reach 100% relative humidity, however,
		  requires 44mg water to be added per litre of inspired gas. As a consequence,
		  the rate of humidification (QH2O; ml/h) equals 2.64 × V, where V
		  is the minute ventilation. Because minute ventilation during high-frequency
		  ventilation ranges between 20 and 40 l/min, QH2O may vary between 50
		  and 100 ml/h. Of course, any change in the ventilatory parameters (tidal volume,
		  ventilation frequency per min, driving pressure, I:E) modifies minute
		  ventilation and, therefore, QH2O. These basic physical principles of
		  humidification are well known, and are accepted in ventilation therapy. The
		  saline solution was warmed by a fluid warmer to 39°C before it reached the
		  jet adapter, allowing for a possible warm up of 42°C if necessary, to
		  compensate for the temperature drop of the gas after decompression
		  (Joule-Thompsen effect) and possible epithelial lesions.
In fact, increasing the temperature of the inspired gas delivered
		  during high-frequency jet ventilation from 39°C–42°C might appear
		  insufficient. After decompression of the gas into the trachea, there is a
		  sudden drop in the temperature of 5–10°C. As a consequence, to reach
		  37°C in the tracheobronchial tree, inspired gas should be warmed to at
		  least 45°C.
In the face of this argument, our humidification system seems to face
		  a serious drawback by providing insufficient temperature of the inspired gas,
		  especially in terms of inducing lesions in the tracheobronchial tree after a
		  prolonged period of SHFJV. However, our period of observation covered
		  approximately 4 days and no signs of persisting inflammation or even necrotizing
		  tracheobronchitis were observed in any group; only tracheobronchial damage
		  (epithelial lesions and transitory inflammation) were detected. These
		  alterations could be compensated for by increasing the humidification rate
		  (Table 3) of the additional humidification system, which
		  differed more than 50% from patient to patient.
The etiology of these different demands can be seen in the
		  multifactorial reasons that influence it, the most important of which is the
		  drift of the so-called isothermic saturation boundary (ISB). This boundary
		  usually lies above the carina during spontaneous breathing and represents the
		  point where the inspired air is fully saturated with vapor and has a
		  temperature of 36°C. Turbulent flow also changes to laminar flow below
		  this point [24], and intubation and ventilation bring
		  this ISB further back along the tracheobronchial tract. Thus, the ability of
		  the lungs to facilitate an adequate temperature and amount of moisture in the
		  inspiration gas is dramatically impaired, leading to the problems that are
		  associated with inadequate humidification and warming.
At present, equipment to monitor humidity is not sufficiently
		  sophisticated to allow accurate breath to breath measurements of humidity
		  within the airway. The estimation of humidification requirements must therefore
		  be based on scientific evidence and clinical impression. Humidification of
		  inspired gases should not be considered in isolation but as part of total
		  airway management. It should be associated with careful fluid balance,
		  physiotherapy, bronchial aspiration and appropriate drug therapy.
Functional studies [24,25] have shown adverse effects of dry inspiratory gas on the
		  tracheal mucosa during ventilation. Chalon et al [12] studied the cytology of epithelial cells from tracheal
		  washings taken during anesthesia via an endotracheal tube with gases at
		  different humidities. Abnormal cytology was found within 2h of ventilation with
		  dry gas but not at 60% humidity or higher. Doyle et al [18] demonstrated that extensive epithelial damage to the
		  trachea with destruction of the cilia, tissue inflammation and necrosis
		  occurred after 72h of CMV with dry gas, but no damage was observed at high
		  humidity. Other studies concerning jet ventilation [26,27] demonstrated epithelial damage
		  at the level of the carina and left and right main-stem bronchus. There are
		  multiple effects of passing warm, dry gas over the tracheal mucosa. Initially,
		  there is an increase in blood supply to this region [28], probably as a result of release of local vasodilators
		  [29]. Subsequently, there is an increase in the
		  osmolality of the mucus secretion as the airway mucosa humidifies the gas
		  before it enters the lungs [30]. Mucus secretions are
		  under parasympathetic control and increase in volume after vagal nerve
		  stimulation [31] or acetylcholine treatment [32]. As the mucus secretion becomes increasingly hyperosmolar
		  and dry, it is trapped and encapsulated beneath the surface. Cellular injury
		  occurs and neutrophil sequestration is exaggerated due to the increase in blood
		  supply. In this situation, with aggravating tissue damage, an exsudate is
		  formed that appears as blisters below the mucosal surface. Because of the
		  external force from mechanical ventilation or jet ventilation, the encapsulated
		  mucus penetrates and causes sloughing of the tracheal epithelial cells.
The clinical implications of inadequate humidification during
		  mechanical ventilation or jet ventilation are very important. The use of dry
		  gas during anesthesia is still common during surgical procedures. Furthermore,
		  dry oxygen is used during resuscitation of asphyxiated patients and preterm
		  infants. The use of dry gas during routine respiratory changes may impair
		  already compromised lungs, especially in infants with chronic obtructive
		  pulmonary disease and adults with ARDS. Tarnow-Mordi et al [32,33] showed an increase in the
		  incidence of pneumothorax and chronic lung disease in patients who were
		  ventilated with inspired gas at low temperatures, implying a low inspired
		  absolute humidity. Necrotizing tracheobronchitis [34],
		  which has been described in several ICUs, has also been attributed to low
		  inspired humidity leading to sloughing of tracheal and bronchial cells [35]. Buchdahl et al [36]
		  showed an increase in chronic upper respiratory tract problems in children with
		  reduced ciliary beat frequency. Damage to the tracheal mucosa occurs during
		  endotracheal intubation and ventilation whatever the inspired humidity. Using
		  dry inspired gas the damage is dramatically worse; therefore, clinical
		  procedures should aim to reduce the use of dry gases in ventilator
		  circuits.
Warming of the inspiration gas is just as important as its
		  humidification to avoid bronchotracheal damage. A lack of warming of the
		  inspired gas is said to be responsible for necrotizing tracheobronchitis among
		  many other cofactors, especially under treatment with HFJV [37,38]. However, Keszler et al
		  [39] showed in a multicenter clinical trial that the
		  incidence of necrotizing tracheobronchitis is similar comparing HFJV with CMV
		  in neonates.
Although multiple factors are associated with necrotizing
		  tracheobronchits, Hanson et al [40] proposed
		  that regional or generalized airway ischemia was the mechanism for airway
		  damage, based on the appearance of mucosal damage with a lack of warming.
Cavanagh et al [41] found an increase
		  in regional tracheal blood flow (10.3-fold), measured by radioactive
		  microspheres, under HFJV compared with spontaneous breathing, increasing
		  further when using dry gas at 22°C. The authors claim the enhanced local
		  hyperemia effect is because of greater water and heat extraction. A moderate
		  hyperventilation that occurred during high-frequency jet ventilation in this
		  study [41] might also have affected tracheal blood flow,
		  although the authors concede that the hyperemia effects appear to relate to
		  shear stress and water removal rather than alveolar partial pressure of carbon
		  dioxide. They found blood flow improvements in the tracheal mucosa, with the
		  highest increase using dry gas.
Although the study by Cavanagh et al covers only a period of
		  2.5 h, another study [42] shows that longer periods of
		  ventilation (33 h) produce no significant differences in airway damage when
		  comparing CMV with HFJV.
Another explanation for the hyperemia effects under HFJV is given by
		  Baile et al [43]. They claim that greater shear
		  stresses with HFJV may also alter mucosal epithelia permeability and
		  secondarily affect the blood flow.
Our study showed that, by providing proper humidification and warming
		  of the inspiration gases, epithelial damage to the tracheobronchial mucosa can
		  be prevented, as can possible inflammation and necrotizing tracheobronchitis,
		  even in long-term applications.
The damage to the mucosa observed in patients in group B relates well
		  with the outcome of the studies by Rouby et al [7,8] and Chatburn and McClellan [19], who have made a very interesting contribution to the
		  problems associated with humidification and warming of high-frequency jet
		  ventilation. Doyle et al [18] and Chatburn and
		  McClellan [19] showed that, by providing adequate
		  moisture and proper temperature of the inspiration gases, deleterious effects
		  on the tracheobronchial mucosa can be prevented. Although their mechanical
		  expenditures and material costs were much higher than ours, the outcome of
		  their studies were just as satisfactory as the results of this study. SHFJV has
		  been shown to be a serious alternative to CMV. Using the Alexander 1, the
		  problems of humidification and warming of the ventilation gas can be handled
		  very well.

Question: Compared to electronic jet-ventilator either with (group A)  group C received high-frequency percussive ventilation (HFPV) by a pneumatic high-frequency respirator, using a hot water humidifier for warming and moistening the inspiration gas. Group D received conventional mechanical ventilation using a standard intensive care unit respirator with a standard humidification system. what was the result of  without an additional humidification system (group B) on temperature measured inside the tube after 2 days?
Evidence: A significantly low inspiration gas temperature was noted in
				patients in group B, initially (27.2 ± 2.5°C) and after 2 days
				(28.0 ± 1.6°C) (P 
Answer: significantly decreased