Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992 29
ENT
surgery
and cystic fibrosis
A Richard Maw MS FRCS Department of Otolaryngology, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW Keywords: cystic fibrosis; hearing loss; sinusitis; nasal polyposis; secretory otitis media
Introduction Whereas there is a loss of sodium and chloride from sweat glands in the skin, there is an increased viscosity of the secretion from mucous glands of the respiratory tract mucosa causing intraduct stagnation and obstruction. Ultimately there is dilatation ofthe tubules and glandular acini. Hyperviscous secretions dry out within the ducts of the glands leading to secondary obstruction and infection. Tlhe hyperviscosity may be due to a change in water or electrolyte content, alteration in glycoprotein secretion, or possibly a defect in sympathetic autonomic innervation. The underlying mucociliary structure and function is normal until it is altered by secondary infection. It is on the basis of these underlying changes that the ENT manifestations of cystic fibrosis (CF) develop. It is relatively rare for such cases to present initially to ENT departments. Nowadays most have been diagnosed as a consequence of chronic progressive pulmonary disease or gastrointestinal problems affecting the pancreas and biliary tract. Nevertheless, occasionally children with chronic cough presenting to ENT departments are found to have a positive sweat test, confirming previously undiagnosed CF. Such children may be confused with those suffering from asthma; sinusitis with a post nasal drip; chronic bronchitis from other causes; gastro-oesophageal reflux; vascular aberration; and less often, previously undiagnosed subglottic stenosis; tracheo malacia; bronchogenic cysts and foreign
bodies'. Most commonly there are signs and symptoms within the nasal passages and sinuses which result from the underlying changes within the mucous glands and ducts. Less frequently, there may be abnormalities in the larynx and salivary glands. It is now accepted that aural changes seen in patients with CF are incidental rather than causally related. Nasal and sinus pathology Clinically, apart from obstruction, CF patients have relatively few nasal and sinus symptoms. However, radiological studies of the sinuses with plain radiographs invariably show widespread abnormalities. Routine occipitomental and occipitofrontal sinus views to demonstrate the antra, ethmoids and frontal sinuses almost always show changes, even at an early age2. Usually the antra and ethmoids show opacification and typically there is failure of pneumatization of the frontal sinuses. Occasionally an ethmoid mucocele or pyocele is present. In such children, diagnosis of these conditions is virtually pathognomonic of CF and confirmatory sweat testing is required3. The plain radiological changes may be due to vasomotor change, polyposis, often with cystic
change, sinusitis or mucocele formation. The failure of pneumatization of the frontal sinuses may be associated with some reduced pneumatization of the antra. Thus there may be a small sinus together with thickened lining mucosa, both giving rise to generalized radiological opacification. The mucous glands within the maxillary sinus demonstrate identical histological changes to the glands in the lower respiratory tract. They are hyperplastic and there is dilatation ofthe tubules and acini. However, within the sinuses, glands are only found in significant numbers around the ostia, whereas in the remaining part of the sinuses, glands are sparse. There are fewer mucous glands within the maxillary sinus than in the nasal mucosa (0.2 glands/mm3 compared with 8.0 glands/mm3)4. It is thought that the mucous membrane within the sinus is altered by infection in the perinatal period, leading to thickening and changes which affect sinus development. At birth the frontal sinuses are not developed and the maxillary sphenoid and ethmoid sinuses are small. The failure of pneumatization of the frontal sinus is thought to be a secondary phenomenon which follows early postnatal changes in the mucous glands around the sinus ostium. This produces thickening and reduced ventilation which ultimately leads to reduced pneumatization of the sinus. There may be similar but radiologically less obvious changes affecting the antra, ethmoids and sphenoid sinuses. The bony walls of the sinuses remain thicker and within the sinuses the mucosa is also thickened. It is these changes together which cause the opacification on plain sinus radiograph, which may be present even in the absence of infection. Indeed, maxillary sinus opacification is virtually universal in CF, whereas only very few patients have severe clinical symptoms of sinusitis. Mucoceles may occur in as many as 20% of cases, and as they enlarge or if they become infected as mucopyoceles, they may produce sinus and orbital symptoms, and may also be the cause of radiological opacification. The introduction of CT scanning has led to the demonstration of changes within the mucosa of the sinuses not shown on plain radiographs but graphically demonstrated by computerized tomography. CT scanning in axial and coronal planes to demonstrate the antra and ethmoid has shown more precisely the differences between the bony changes within the walls of the sinuses and the mucosal change within the sinus cavities. However, even in patients without CF, it has always been accepted that many of the changes of polypoid mucosal thickening seen on plain radiographs were not of clinical significance. With CT in an asymptomatic, non cystic paediatric population, abnormalities have been shown
30 Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992
in 18% of cases5, and in 15% of children over the age of 12 years6. In symptomatic, non cystic patients with sinus related problems, CT abnormalities are seen in more than 40% of cases7. Sinonasal disease was found to be ubiquitous in children with cystic fibrosis evaluated with coronal CT scanning8. Great caution is required in interpreting these more obvious radiological changes shown by CT scanning and such appearances need close correlation with any nasal or sinus symptoms which may be present. Coronal CT scanning has drawn attention to the middle meatus beneath the middle turbinate, wherein lie the ostia of the maxillary, frontal, and the anterior and middle ethmoid air cell systems. Obstructive pathology within the middle meatus from a variety of causes is now known to be responsible for extensive changes within the sinuses. The advent of rigid endoscopic examination ofthe nasal passages, and the middle meatus in particular, has confirmed previously undiagnosed mucosal disease. Changes may be found in the agger nasi cells, anterior and superior to the insertion of the middle turbinate at the lateral nasal wall. There may be variations of the uncinate process which may be curved medially, laterally or anteriorly, obstructing the entrance to the middle -meatus. Like the middle turbinate, the uncinate process may also in some cases be pneumatized. The ethmoid bulla may also be extensively pneumatized and may obstruct the ethmoid infundibulum and thus the drainage of the maxillary sinus. It is now accepted that disease within this confined osteo-meatal complex of the middle meatus is the key to sinus pathology within the antra, ethmoids and frontal sinuses9. The alterations in the mucous glands and mucosa in and around the sinus ostia in very early childhood in patients with CF may be the cause of later radiological changes seen within the sinuses which then become the focus of medical and surgical attention in later childhood and thereafter. Magnetic resonance imaging (MRI) also demonstrates paranasal sinus pathology with remarkable clarity'0. However, unlike CT scanning, the bony changes are less well defined. Even in patients without CF and those not suffering intercurrent colds, MRI changes within the sinuses can be demonstrated in 25-37% of examinations of the head performed for indications not associated with sinus pathology. Thus such changes, even in normal individuals, are unrelated to the patients presenting problems and probably are of no consequence. Such changes seen on MRI are most frequent in the maxillary and ethmoid sinuses, and least frequent in the frontal and sphenoid sinuses. If changes of minimal mucosal thickening are excluded, 17% of cases in a recent prospective study showed either fluid or marked mucosal thickening in at least one ofthe sinuses scanned. In this prospective study of non cystic patients, nasal symptoms, other than the presence of a cold, showed no relationship to MRI findings. Sixty-five per cent of patients with a cold had positive MRI compared with 34% who did not+"
Nasal polyposis Various reported studies suggest that nasal polyposis occurs in 6-36% of cases with CF and occurs most frequently in children aged between 4 and 12 years'12"3. As nasal polyps are relatively rare in nonaffected children, any child presenting with nasal polypi should have a sweat test to exclude CF. The
polypi are frequently multiple and bilateral, and they recur frequently after removal. Some surveys of patients with CF and nasal polyposis confirm allergy in up to half of the cases, but it seems likely that infection is an equally important causative factor for the development of nasal polypi in these cases. Histologically, polypi are the same in patients with or without CF. The number and density of the mucous glands within the polypi have been shown by Tos to be identical in those with and without CF, and it seems that the pathogenesis of nasal polypi is the same in cystic fibrotics as in patients suffering with allergy or infection'2. The chest and larynx The effects of the chronic progressive pulmonary disease caused by increased viscosity of the secretions in the lower respiratory tract are dealt with elsewhere. There are few symptoms from changes in the mucous glands in the nasopharynx or pharyngolarynx. However, the pulmonary artery hypertension and dilatation which occurs in 70% of patients with cystic fibrosis may very occasionally lead to recurrent laryngeal nerve paresis and hoarseness14.
Salivary gland The same changes which occur within the pancreatic glandular tissue are also seen in the salivary glands where there is occlusion ofthe ducts by hyper-viscous secretions. Such changes are said to be more common in the sub-mandibular salivary gland. Electrolyte changes in the secretions of the salivary glands are similar to those seen in sweat, with elevation of sodium and chloride. These changes are rarely of clinical significance. Eustachian tube and middle ear Normally, mucous production within the middle ear is minimal, for the mucosa of the middle ear cleft and mastoid air cell system is a single layer of flat respiratory cells with very few goblet cells. This is true of the bony part of the Eustachian tube but not the mucosa of the pharyngeal part of the tube where there are both goblet cells and mucous glands in the sub-mucosa, identical to those of the lower respiratory tract. Therefore, it is only in this part of the Eustachian tube that one should anticipate glandular changes associated with CF. There are variable reports in the literature of middle ear involvement in patients with CF. The initial studies were of small numbers without objective tympanometric confirmation of middle ear abnormality. It is now known that the prevalence of secretory otitis or glue ear in CF is no higher than in individuals without the disease'5. Furthermore, middle ear pressure measurements in affected children are the same as those without the condition'6. Thus, secretory otitis media is not more common in children with CF. In support of the negative effect of CF on middle ear function, Todd has shown that average mastoid pneumatization volume was larger for CF patients than for normal controls17. Moreover, there is no evidence that acute suppurative otitis media is more frequent in patients with the disease. Consequently, chronic suppurative otitis media as a sequel of these preceding conditions is also no more common than in the general population.
Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992 31
Sensory neural hearing loss Hearing impairment affecting the inner ear may develop during the treatment of CF. It is usually in the high frequencies and is most frequently bilateral. It is not a consequence ofthe disease itself but results from damage to the hairells from aminoglycoside antibiotics such as gentamycin and tobramyciul8. It is more common in the presence of impaired renal function. Careful monitoring with serial audiometry during treatment should reduce- the incidence of this complication, and an early Warning of cochlear damage during medication can be gained by monitoring electrocochleographic and auditory brain stem responses, and high frequency hearing thresholds between 8000 and 20 000 Hertz19. Medical management Diagnosis In ENT practice CF should be suspected in all chil4ren with otherwise undiagnosed chronic cough, or in children presenting with nasal polyposis. Children with relatively few nasal or sinus sptms but with opaque maxillary or ethmoid sintses on plain radiograph should be suspected of suffering from CF, as should those with an obvious mucocele or mucopyocele. Such changes can be verifed on CT scanning or MRI, but the results need to be interpreted with great caution, bearing in mind- the large number of patients without CF who show inconsequential nasal and sinus mucosal- changes with these -imaging techniques. Rigid endoscopic examination ofthe nasal passages may aid conventional clinical examination with a nasal speculum. Treatment The ENT manifestations of changes in patients with CF should be managed in an identical manner to those not suffering from the condition. Appropriate antibiotic treatment for the chest condition should be effective for nasal and sinus infection, provided drainage is achieved and there is not blockage in the middle meatus. In this way any sanctuary, particularly for Pseudornonas aeruginosa, within the sinuses should receive appropriate medication. Nasopharyngeal sampling may reveal the most information about pseudomonas infection in patients with CF20. Mucosal thickening and minor polyposis within the nasal passages can be treated with intranasal steroid insufflation using beclomethasone, or similar steroid preparations, and these have been shown to have a beneficial effect subjectively21. Plain Betnesol drops instilled in the prone position are appropriate for polyposis located high in the nasal passages. Such treatment will not achieve clearance of an obstructed nasal airway but will serve to maintain a patent airway once partial or total clearance has been achieved.
Surgery Nasal and sinus surgery should be severely restricted in these patients and, where possible, general anaesthesia avoided. Antral washout should not be carried out on the basis of opacity of the antra, for frequently the radiological changes on which this surgical judgement is made reflect mucosal thickening rather than the presence of pus. Similarly, placement of indwelling, intrasinus tubes for repeated washouts is probably not of long term benefit and has not as yet been proven with any
satisfactory study. No obvious correlation between cultures from sinus washouts ard corresponding sputum samples have been shown in patients with CF and nasal polyposis2. Nasal polypi should be removed surgically only when tli&ey cause significant or total blockage of the nasal passages. If removal is not carried out, secondary obstructive sinus symptoms can develop. Moreover, expansion of the nasal bones with nasal -deformity can ensue- in some cases. Tos states that generally speaking nasal and sinus surgery should be restricted'2. It is unlikely that conventional intranaial antrostomy in the inferior meatus is helpful- as a routine procedure in these cases. Likewise, a Caldwell-Luc operation to fashion such an antkostomy should be avoided. Ethminidmy surgery, whether via an intranasal, 4xtenU1 or transantral route should be avoided if possible. Nevertheless, there are oppoeite views, often based; on experience with relatively few cases, suggesting fewerrecurrences of polyposis and longer symptom--free intervals following more extensive sinus surgery92. Reduction in headache, respiratory symptoms and frequency of hospital admissions were -suggested to result from a combination of bilateral Caldwell-Luc procedures with pe-oriperative, anti_pseudomonas treatment, but in a study of only four adult CF patients24. There have been recent reports of treatment to the osteomeatal complex of the -middle meatus hy functional endoscopic sinus surgery (FES). This type of procedure has a more physiological approach to maxillary and ethmoid sinus ainage but is still unproven in terms of 'producing significant, sustained benefit and, again, should be advised with caution25. It is, however, a means of removing middle meatal polypi with minimal damage to the remaining mucosa, and with this technique an antrostomy can be fashioned in the middle meatus at the site of the physiological point of drainage of the maxillary, anterior and middle ethmoid sinuses. More precise surgical removal of abnormal polypoid mucosa can be achieved for there is direct endoscopic observation whilst the surgery is being performed. Mucoceles and mucopyoceles require treatment as in patients without CF. Surgery to the ear should be carried as for nonaffected patients and adenoidectomy, unless for gross airway obstruction confirmed radiologically and in the presence of severe clinical symptoms such as obstructive sleep apnoea, should not be performed. Likewise, tonsillectomy should only be advised for indications which would merit operation in nonaffected patients. In summary, surgical treatment for patients with CF should be advised with caution26. It is unlikely that, apart from removal of obstructing nasal polypi, elective surgery to the nose or sinuses in these patients will have any long term benefit in their overall management. As in patients not suffering with CF, each new advance in surgical treatment will tend to be applied to such patients, and this would appear from the literature to be the situation with respect to functional endoscopic sinus surgery. Hopefully, after the anticipated rash of publications, this excellent technique will be recommended for this type of patient in the same manner as it is recommended for those not suffering with CF.
32 Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992
References 1 Holinger LD, Sanders AD. Chronic cough in infants and children: an update. Laryngoscope 1991;191:596-605 2 Adams GL, Hilger P, Warwick WF. Cystic fibrosis. Arch Otolaryngol 1980;106:127-32 3 Gutterplan MD, Wetmore RF. Paranasal sinus mucocele in cystic fibrosis. Clin Pediatr (Phila) 1989;28: 429-30 4 Tos M. Goblet cells and glands in the nose and paranasal sinuses. In: Proctor D, Andersen J, eds. The nose: upper airway physiology and the atmospheric environment. Amsterdam: Elsevier, 1982:99 5 Diament M, Senac M, Gilsanz V, Baker S, Gillespie T, Larsson S. Prevalence of incidental paranasal sinuses opacification in pediatric patients: a CT study. J Comput Assist Tomogr 1987;11:426-31 6 Glasier C, Ascher D, Williams K. Incidental paranasal sinus abnormalities on CT of children: clinical correlation. Am J Neuroradiol 1986;7:861-4 7 Havas T, Motbey J, Gullane P. Prevalence of incidental abnormalities on computed tomographic scans of the paranasal sinuses. Arch Otolaryngol 1988;114:856-9 8 Cuyler JP, Monaghan AJ. Cystic fibrosis and sinusitis. J Otolaryngol 1989;18:173-5 9 Stammberger H, Wolf G. Headaches and sinus disease. The endoscopic approach. Ann Otol Rhinol Laryngol 1988;97(suppl 134):1-23 10 Moser FG, Panush D, Rubin JS, Honigsberg RM, Sprayregen S, Eisig SB. Incidental paranasal sinus abnormalities on MRI of the brain. Clin Radiol 1991;43:252-4 11 Cooke LD, Hadley DM. Incidental abnormalities ofthe paranasal sinuses detected by magnetic resonance imaging. Presented at Eighth British Academic Conference in Otolaryngology, Dublin, 1991 12 Tos M. Cystic fibrosis (mucoviscidosis). In: English GM, ed. Diseases of the nose and sinuses, vol 2. Philadelphia: Lippincott 1990:11 13 Cepero R, Smith RJ, Catlin FI, Bressler KL, Furuta GT, Shandera KC. Cystic fibrosis: an otolaryngologic perspective. J Otolaryngol Head Neck Surg 1987;97: 356-60
14 Zitsch RP, Reilly JS. Vocal cord paralysis associated with cystic fibrosis. Ann Otol Rhinol Laryngol 1987;96:680-3 15 Forman-Franco B, Abramson AL, Gorvoy JD, Stein T. Cystic fibrosis and hearing loss. Arch Otolaryngol 1979;105:338-42 16 Bak-Pedersen K, Larsen PK. Inflammatory middle ear disease in patients with cystic fibrosis. Acta Otolaryngol (Stockh) 1979;Suppl 360:138-40 17 Todd NW, Martin WS. Temporal bone pneumatization in cystic fibrosis patients. Laryngoscope 1988;98:1046-9 18 Thomsen J, Friis B, Jensen K, Bak Pedersen K, Larsen PK. Tobramycin ototoxicity: repeated courses of high dosage treatment in children with cystic fibrosis. J Antimicrob Chemother 1979;5:257-60 19 McRorie TI, Bosso J, Randolf L. Aminoglycoside ototoxicity in cystic fibrosis. Evaliation by high firquency audiometry. Am JDis Child 1989;143:1328-32 20 Morgan DW, Taylor RFH, Nicholson PF, Mackay IS, Hodson ME, Pitt TL. Cystic fibrosis: sanctuary sites for P aeruginosa in adult patients. Clin Otolaryngol 1991; (in press) 21 Donaldson JD, Gillespie CT. Observations on the efficacy of intra-nasal beclomethasone diproprionate in cystic fibrosis patients. J Otolaryngol 1988;17:43-5 22 Drake-Lee AB, Morgan DW. Nasal polyps and sinusitis in children with cystic fibrosis. J Laryngol Otol 1989;103:753-5 23 Crockett DM, McGill TJ, Healy GB, Friedman EM, Salkeld LJ. Nasal and paranasal sinus surgery in children with cystic fibrosis. Am Otol Rhinol Laryngol 1987;96:367-72 24 Umetsu DJ, Moss RB, King VV, Lewiston NJ. Sinus disease in patients with severe cystic fibrosis: relation to pulmonary exacerbation. Lancet 1990;335:1077-8 25 Duplechain JK, White JA, Muller RH. Pediatric sinusitis. The role of endoscopic sinus surgery in cystic fibrosis and other forms of sinonasal disease. Arch Otolaryngol Head Neck Surg 1991;117:422-6 26 David TJ. Nasal polyposis, opaque paras sinuses and usually normal hearing: the otorhino laryngo logical features of cystic fibrosis. JR Soc Med 1986;79(suppl 12): 23-6
ENT
surgery
and cystic fibrosis
A Richard Maw MS FRCS Department of Otolaryngology, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW Keywords: cystic fibrosis; hearing loss; sinusitis; nasal polyposis; secretory otitis media
Introduction Whereas there is a loss of sodium and chloride from sweat glands in the skin, there is an increased viscosity of the secretion from mucous glands of the respiratory tract mucosa causing intraduct stagnation and obstruction. Ultimately there is dilatation ofthe tubules and glandular acini. Hyperviscous secretions dry out within the ducts of the glands leading to secondary obstruction and infection. Tlhe hyperviscosity may be due to a change in water or electrolyte content, alteration in glycoprotein secretion, or possibly a defect in sympathetic autonomic innervation. The underlying mucociliary structure and function is normal until it is altered by secondary infection. It is on the basis of these underlying changes that the ENT manifestations of cystic fibrosis (CF) develop. It is relatively rare for such cases to present initially to ENT departments. Nowadays most have been diagnosed as a consequence of chronic progressive pulmonary disease or gastrointestinal problems affecting the pancreas and biliary tract. Nevertheless, occasionally children with chronic cough presenting to ENT departments are found to have a positive sweat test, confirming previously undiagnosed CF. Such children may be confused with those suffering from asthma; sinusitis with a post nasal drip; chronic bronchitis from other causes; gastro-oesophageal reflux; vascular aberration; and less often, previously undiagnosed subglottic stenosis; tracheo malacia; bronchogenic cysts and foreign
bodies'. Most commonly there are signs and symptoms within the nasal passages and sinuses which result from the underlying changes within the mucous glands and ducts. Less frequently, there may be abnormalities in the larynx and salivary glands. It is now accepted that aural changes seen in patients with CF are incidental rather than causally related. Nasal and sinus pathology Clinically, apart from obstruction, CF patients have relatively few nasal and sinus symptoms. However, radiological studies of the sinuses with plain radiographs invariably show widespread abnormalities. Routine occipitomental and occipitofrontal sinus views to demonstrate the antra, ethmoids and frontal sinuses almost always show changes, even at an early age2. Usually the antra and ethmoids show opacification and typically there is failure of pneumatization of the frontal sinuses. Occasionally an ethmoid mucocele or pyocele is present. In such children, diagnosis of these conditions is virtually pathognomonic of CF and confirmatory sweat testing is required3. The plain radiological changes may be due to vasomotor change, polyposis, often with cystic
change, sinusitis or mucocele formation. The failure of pneumatization of the frontal sinuses may be associated with some reduced pneumatization of the antra. Thus there may be a small sinus together with thickened lining mucosa, both giving rise to generalized radiological opacification. The mucous glands within the maxillary sinus demonstrate identical histological changes to the glands in the lower respiratory tract. They are hyperplastic and there is dilatation ofthe tubules and acini. However, within the sinuses, glands are only found in significant numbers around the ostia, whereas in the remaining part of the sinuses, glands are sparse. There are fewer mucous glands within the maxillary sinus than in the nasal mucosa (0.2 glands/mm3 compared with 8.0 glands/mm3)4. It is thought that the mucous membrane within the sinus is altered by infection in the perinatal period, leading to thickening and changes which affect sinus development. At birth the frontal sinuses are not developed and the maxillary sphenoid and ethmoid sinuses are small. The failure of pneumatization of the frontal sinus is thought to be a secondary phenomenon which follows early postnatal changes in the mucous glands around the sinus ostium. This produces thickening and reduced ventilation which ultimately leads to reduced pneumatization of the sinus. There may be similar but radiologically less obvious changes affecting the antra, ethmoids and sphenoid sinuses. The bony walls of the sinuses remain thicker and within the sinuses the mucosa is also thickened. It is these changes together which cause the opacification on plain sinus radiograph, which may be present even in the absence of infection. Indeed, maxillary sinus opacification is virtually universal in CF, whereas only very few patients have severe clinical symptoms of sinusitis. Mucoceles may occur in as many as 20% of cases, and as they enlarge or if they become infected as mucopyoceles, they may produce sinus and orbital symptoms, and may also be the cause of radiological opacification. The introduction of CT scanning has led to the demonstration of changes within the mucosa of the sinuses not shown on plain radiographs but graphically demonstrated by computerized tomography. CT scanning in axial and coronal planes to demonstrate the antra and ethmoid has shown more precisely the differences between the bony changes within the walls of the sinuses and the mucosal change within the sinus cavities. However, even in patients without CF, it has always been accepted that many of the changes of polypoid mucosal thickening seen on plain radiographs were not of clinical significance. With CT in an asymptomatic, non cystic paediatric population, abnormalities have been shown
30 Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992
in 18% of cases5, and in 15% of children over the age of 12 years6. In symptomatic, non cystic patients with sinus related problems, CT abnormalities are seen in more than 40% of cases7. Sinonasal disease was found to be ubiquitous in children with cystic fibrosis evaluated with coronal CT scanning8. Great caution is required in interpreting these more obvious radiological changes shown by CT scanning and such appearances need close correlation with any nasal or sinus symptoms which may be present. Coronal CT scanning has drawn attention to the middle meatus beneath the middle turbinate, wherein lie the ostia of the maxillary, frontal, and the anterior and middle ethmoid air cell systems. Obstructive pathology within the middle meatus from a variety of causes is now known to be responsible for extensive changes within the sinuses. The advent of rigid endoscopic examination ofthe nasal passages, and the middle meatus in particular, has confirmed previously undiagnosed mucosal disease. Changes may be found in the agger nasi cells, anterior and superior to the insertion of the middle turbinate at the lateral nasal wall. There may be variations of the uncinate process which may be curved medially, laterally or anteriorly, obstructing the entrance to the middle -meatus. Like the middle turbinate, the uncinate process may also in some cases be pneumatized. The ethmoid bulla may also be extensively pneumatized and may obstruct the ethmoid infundibulum and thus the drainage of the maxillary sinus. It is now accepted that disease within this confined osteo-meatal complex of the middle meatus is the key to sinus pathology within the antra, ethmoids and frontal sinuses9. The alterations in the mucous glands and mucosa in and around the sinus ostia in very early childhood in patients with CF may be the cause of later radiological changes seen within the sinuses which then become the focus of medical and surgical attention in later childhood and thereafter. Magnetic resonance imaging (MRI) also demonstrates paranasal sinus pathology with remarkable clarity'0. However, unlike CT scanning, the bony changes are less well defined. Even in patients without CF and those not suffering intercurrent colds, MRI changes within the sinuses can be demonstrated in 25-37% of examinations of the head performed for indications not associated with sinus pathology. Thus such changes, even in normal individuals, are unrelated to the patients presenting problems and probably are of no consequence. Such changes seen on MRI are most frequent in the maxillary and ethmoid sinuses, and least frequent in the frontal and sphenoid sinuses. If changes of minimal mucosal thickening are excluded, 17% of cases in a recent prospective study showed either fluid or marked mucosal thickening in at least one ofthe sinuses scanned. In this prospective study of non cystic patients, nasal symptoms, other than the presence of a cold, showed no relationship to MRI findings. Sixty-five per cent of patients with a cold had positive MRI compared with 34% who did not+"
Nasal polyposis Various reported studies suggest that nasal polyposis occurs in 6-36% of cases with CF and occurs most frequently in children aged between 4 and 12 years'12"3. As nasal polyps are relatively rare in nonaffected children, any child presenting with nasal polypi should have a sweat test to exclude CF. The
polypi are frequently multiple and bilateral, and they recur frequently after removal. Some surveys of patients with CF and nasal polyposis confirm allergy in up to half of the cases, but it seems likely that infection is an equally important causative factor for the development of nasal polypi in these cases. Histologically, polypi are the same in patients with or without CF. The number and density of the mucous glands within the polypi have been shown by Tos to be identical in those with and without CF, and it seems that the pathogenesis of nasal polypi is the same in cystic fibrotics as in patients suffering with allergy or infection'2. The chest and larynx The effects of the chronic progressive pulmonary disease caused by increased viscosity of the secretions in the lower respiratory tract are dealt with elsewhere. There are few symptoms from changes in the mucous glands in the nasopharynx or pharyngolarynx. However, the pulmonary artery hypertension and dilatation which occurs in 70% of patients with cystic fibrosis may very occasionally lead to recurrent laryngeal nerve paresis and hoarseness14.
Salivary gland The same changes which occur within the pancreatic glandular tissue are also seen in the salivary glands where there is occlusion ofthe ducts by hyper-viscous secretions. Such changes are said to be more common in the sub-mandibular salivary gland. Electrolyte changes in the secretions of the salivary glands are similar to those seen in sweat, with elevation of sodium and chloride. These changes are rarely of clinical significance. Eustachian tube and middle ear Normally, mucous production within the middle ear is minimal, for the mucosa of the middle ear cleft and mastoid air cell system is a single layer of flat respiratory cells with very few goblet cells. This is true of the bony part of the Eustachian tube but not the mucosa of the pharyngeal part of the tube where there are both goblet cells and mucous glands in the sub-mucosa, identical to those of the lower respiratory tract. Therefore, it is only in this part of the Eustachian tube that one should anticipate glandular changes associated with CF. There are variable reports in the literature of middle ear involvement in patients with CF. The initial studies were of small numbers without objective tympanometric confirmation of middle ear abnormality. It is now known that the prevalence of secretory otitis or glue ear in CF is no higher than in individuals without the disease'5. Furthermore, middle ear pressure measurements in affected children are the same as those without the condition'6. Thus, secretory otitis media is not more common in children with CF. In support of the negative effect of CF on middle ear function, Todd has shown that average mastoid pneumatization volume was larger for CF patients than for normal controls17. Moreover, there is no evidence that acute suppurative otitis media is more frequent in patients with the disease. Consequently, chronic suppurative otitis media as a sequel of these preceding conditions is also no more common than in the general population.
Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992 31
Sensory neural hearing loss Hearing impairment affecting the inner ear may develop during the treatment of CF. It is usually in the high frequencies and is most frequently bilateral. It is not a consequence ofthe disease itself but results from damage to the hairells from aminoglycoside antibiotics such as gentamycin and tobramyciul8. It is more common in the presence of impaired renal function. Careful monitoring with serial audiometry during treatment should reduce- the incidence of this complication, and an early Warning of cochlear damage during medication can be gained by monitoring electrocochleographic and auditory brain stem responses, and high frequency hearing thresholds between 8000 and 20 000 Hertz19. Medical management Diagnosis In ENT practice CF should be suspected in all chil4ren with otherwise undiagnosed chronic cough, or in children presenting with nasal polyposis. Children with relatively few nasal or sinus sptms but with opaque maxillary or ethmoid sintses on plain radiograph should be suspected of suffering from CF, as should those with an obvious mucocele or mucopyocele. Such changes can be verifed on CT scanning or MRI, but the results need to be interpreted with great caution, bearing in mind- the large number of patients without CF who show inconsequential nasal and sinus mucosal- changes with these -imaging techniques. Rigid endoscopic examination ofthe nasal passages may aid conventional clinical examination with a nasal speculum. Treatment The ENT manifestations of changes in patients with CF should be managed in an identical manner to those not suffering from the condition. Appropriate antibiotic treatment for the chest condition should be effective for nasal and sinus infection, provided drainage is achieved and there is not blockage in the middle meatus. In this way any sanctuary, particularly for Pseudornonas aeruginosa, within the sinuses should receive appropriate medication. Nasopharyngeal sampling may reveal the most information about pseudomonas infection in patients with CF20. Mucosal thickening and minor polyposis within the nasal passages can be treated with intranasal steroid insufflation using beclomethasone, or similar steroid preparations, and these have been shown to have a beneficial effect subjectively21. Plain Betnesol drops instilled in the prone position are appropriate for polyposis located high in the nasal passages. Such treatment will not achieve clearance of an obstructed nasal airway but will serve to maintain a patent airway once partial or total clearance has been achieved.
Surgery Nasal and sinus surgery should be severely restricted in these patients and, where possible, general anaesthesia avoided. Antral washout should not be carried out on the basis of opacity of the antra, for frequently the radiological changes on which this surgical judgement is made reflect mucosal thickening rather than the presence of pus. Similarly, placement of indwelling, intrasinus tubes for repeated washouts is probably not of long term benefit and has not as yet been proven with any
satisfactory study. No obvious correlation between cultures from sinus washouts ard corresponding sputum samples have been shown in patients with CF and nasal polyposis2. Nasal polypi should be removed surgically only when tli&ey cause significant or total blockage of the nasal passages. If removal is not carried out, secondary obstructive sinus symptoms can develop. Moreover, expansion of the nasal bones with nasal -deformity can ensue- in some cases. Tos states that generally speaking nasal and sinus surgery should be restricted'2. It is unlikely that conventional intranaial antrostomy in the inferior meatus is helpful- as a routine procedure in these cases. Likewise, a Caldwell-Luc operation to fashion such an antkostomy should be avoided. Ethminidmy surgery, whether via an intranasal, 4xtenU1 or transantral route should be avoided if possible. Nevertheless, there are oppoeite views, often based; on experience with relatively few cases, suggesting fewerrecurrences of polyposis and longer symptom--free intervals following more extensive sinus surgery92. Reduction in headache, respiratory symptoms and frequency of hospital admissions were -suggested to result from a combination of bilateral Caldwell-Luc procedures with pe-oriperative, anti_pseudomonas treatment, but in a study of only four adult CF patients24. There have been recent reports of treatment to the osteomeatal complex of the -middle meatus hy functional endoscopic sinus surgery (FES). This type of procedure has a more physiological approach to maxillary and ethmoid sinus ainage but is still unproven in terms of 'producing significant, sustained benefit and, again, should be advised with caution25. It is, however, a means of removing middle meatal polypi with minimal damage to the remaining mucosa, and with this technique an antrostomy can be fashioned in the middle meatus at the site of the physiological point of drainage of the maxillary, anterior and middle ethmoid sinuses. More precise surgical removal of abnormal polypoid mucosa can be achieved for there is direct endoscopic observation whilst the surgery is being performed. Mucoceles and mucopyoceles require treatment as in patients without CF. Surgery to the ear should be carried as for nonaffected patients and adenoidectomy, unless for gross airway obstruction confirmed radiologically and in the presence of severe clinical symptoms such as obstructive sleep apnoea, should not be performed. Likewise, tonsillectomy should only be advised for indications which would merit operation in nonaffected patients. In summary, surgical treatment for patients with CF should be advised with caution26. It is unlikely that, apart from removal of obstructing nasal polypi, elective surgery to the nose or sinuses in these patients will have any long term benefit in their overall management. As in patients not suffering with CF, each new advance in surgical treatment will tend to be applied to such patients, and this would appear from the literature to be the situation with respect to functional endoscopic sinus surgery. Hopefully, after the anticipated rash of publications, this excellent technique will be recommended for this type of patient in the same manner as it is recommended for those not suffering with CF.
32 Journal of the Royal Society of Medicine Supplement No. 19 Volume 85 1992
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